bluuebunny/crossref_metadata_2025_split huggingface dataset:
Key stakeholders’ views, experiences and expectations of patient and public involvement in healthcare professions’ education: a qualitative study
Authors: Cullen Megan , Cadogan Cathal , George Susmi , Murphy Siobhan , Freeney Siobhan , Fitzpatrick Robbie , Strawbridge Judith 
Published: April 2022

Abstract
Background
Patients and the public have an integral role in educating healthcare professionals. Authentic partnerships between higher education institutions and patients and the public are essential. This study examined key stakeholders’ views, experiences and expectations of patient and public involvement (PPI) including the nature of the involvement and requirements for partnership.

Methods
Purposive and snowball sampling was used to recruit key stakeholders, including patients and members of the public involved in health professions education, and academics interested in PPI. Focus groups were held with patient and public participants, providing the opportunity to gain multiple perspectives in an interactive group setting. Academics with an interest in PPI were interviewed using a semi-structured approach. Topic guides were derived from the literature and piloted prior to data collection. Focus groups and interviews were conducted until data saturation was achieved. All data was audio-recorded, transcribed, anonymised and thematically analysed.

Results
Four focus groups were conducted involving 23 patient and public participants (median number of participants per focus group of 6). Nine interviews were conducted with academics (face-to-face [n = 8] or by telephone [n = 1]). Five themes were developed: previous experiences of PPI, training requirements, challenges/barriers to PPI, facilitators of PPI and future ideas for PPI. All participants held positive views of the value of PPI. Participants had mixed views in terms of training, which depended on the level of involvement, but similar views on the challenges and facilitators for PPI in education. There was agreement that PPI requires institutional vision and investment to build strong relationships and a culture of PPI best practice.

Conclusions
There is a need for more strategic and formal involvement of patients and the public to ensure that that PPI becomes sustainably embedded in health professions education.
A healthy dietary metabolic signature is associated with a lower risk for type 2 diabetes and coronary artery disease
Authors: Smith Einar , Ericson Ulrika , Hellstrand Sophie , Orho-Melander Marju , Nilsson Peter M. , Fernandez Céline , Melander Olle , Ottosson Filip 
Published: April 2022

Abstract
Background
The global burden of cardiovascular disease and type 2 diabetes could be decreased by improving dietary factors, but identification of groups suitable for interventional approaches can be difficult. Reporting of dietary intake is prone to errors, and measuring of metabolites has shown promise in determining habitual dietary intake. Our aim is to create a metabolic signature that is associated with healthy eating and test if it associates with type 2 diabetes and coronary artery disease risk.

Methods
Using plasma metabolite data consisting of 111 metabolites, partial least square (PLS) regression was used to identify a metabolic signature associated with a health conscious food pattern in the Malmö Offspring Study (MOS, n = 1538). The metabolic signature’s association with dietary intake was validated in the Malmö Diet and Cancer study (MDC, n = 2521). The associations between the diet-associated metabolic signature and incident type 2 diabetes and coronary artery disease (CAD) were tested using Cox regression in MDC and logistic regression in Malmö Preventive Project (MPP, n = 1083). Modelling was conducted unadjusted (model 1), adjusted for potential confounders (model 2) and additionally for potential mediators (model 3).

Results
The metabolic signature was associated with lower risk for type 2 diabetes in both MDC (hazard ratio: 0.58, 95% CI 0.52–0.66, per 1 SD increment of the metabolic signature) and MPP (odds ratio: 0.54, 95% CI 0.44–0.65 per 1 SD increment of the metabolic signature) in model 2. The results were attenuated but remained significant in model 3 in both MDC (hazard ratio 0.73, 95% CI 0.63–0.83) and MPP (odds ratio 0.70, 95% CI 0.55–0.88). The diet-associated metabolic signature was also inversely associated with lower risk of CAD in both MDC and MPP in model 1, but the association was non-significant in model 3.

Conclusions
In this proof-of-concept study, we identified a healthy diet-associated metabolic signature, which was inversely associated with future risk for type 2 diabetes and coronary artery disease in two different cohorts. The association with diabetes was independent of traditional risk factors and might illustrate an effect of health conscious dietary intake on cardiometabolic health.
Prediction of residual ischemic risk in ticagrelor-treated patients with acute coronary syndrome
Authors: Zou Yuting , Wang Yuyan , Wu Yangxun , Zhang Shizhao , Liu Haiping , Yin Tong 
Published: April 2022

Abstract
Background
Despite strong antiplatelet therapy with ticagrelor, serious ischemic events still occur in patients with acute coronary syndrome (ACS). The predictability of platelet reactivity to the residual risk of ischemic events during ticagrelor treatment remains uncertain.

Objectives
We aimed to investigate the predictability of the thromboelastography (TEG)-measured adenosine disphosphate (ADP)-induced platelet inhibition rate (ADP%) to the ischemic events in ticagrelor-treated patients with ACS.

Methods
A cohort of ticagrelor-treated patients with ACS were consecutively recruited. ADP% was measured by TEG after 3 days of ticagrelor maintenance treatment. The primary ischemic event was defined as rehospitalization for unstable angina (UA) within 1 year, and the secondary ischemic event was a composite of the primary ischemic event plus all-cause death, nonfatal myocardial infarction (MI), stent thrombosis, stroke, and unplanned revascularization within 1 year.

Results
A total of 751 eligible patients with ACS were included in the analysis, with 336 patients randomly assigned to the derivation group and 415 to the validation group. The overall rates of primary and secondary ischemic events were 14.51% (n = 109) and 16.91% (n = 127), respectively. Compared to the patients without ischemic events, those with ischemic events had a significantly lower ADP% both in the derivation group (for primary ischemic events: 66.05% vs. 92.80%, p < 0.001; for secondary ischemic events: 66.05% vs. 93.20%, p < 0.001) and in the validation group (for primary ischemic events: 66.40% vs. 89.20%, p < 0.001; for secondary ischemic events: 66.90% vs. 89.20%, p < 0.001). Receiver operating characteristic curve (ROC) analysis showed that an ADP% < 76% was the optimal cut-off value for predicting 1-year primary ischemic events, with an area under the curve (AUC) of 0.80 (95% CI: 0.72–0.86, p < 0.001) in the derivation group and 0.77 (95% CI: 0.69–0.85, p < 0.001) in the validation group. The multivariate Cox regression hazard analysis consistently identified an ADP% < 76% as an independent predictor of primary ischemic events in the derivation group (HR: 8.21, 95% CI: 4.82–13.99, p < 0.001) and in the validation group (HR: 6.34 95% CI: 3.32–12.11, p < 0.001). There was also a strong association between an ADP% < 76 and the occurrence of secondary ischemic events in the derivation group (HR: 7.33, 95% CI: 4.47–12.00, p < 0.001) and in the validation group (HR: 4.76, 95% CI: 2.73–8.32, p < 0.001).

Conclusion
The ADP-induced platelet inhibition rate measured by TEG could predict ischemic events in ticagrelor-treated patients with ACS.
Quadruple term gestation of quadri-chorionic quadri-amniotic pregnancy after artificial insemination: a case report
Authors: Caballero-Reyes Mauricio , Medina-Rivera Diana , Alas-Pineda César , Mejía-Raudales Beatriz , Gaitán-Zambrano Kristhel , Valle Rubí Tesla 
Published: April 2022

Abstract
Background
To solve infertility, modern science has promoted assisted reproduction techniques such as in vitro fertilization, ovulation induction, and artificial insemination. Quadruple-type multiple pregnancies occur in 1 of every 500,000 pregnancies, and it is estimated that 90% occur due to assisted reproductive techniques, which often lead to numerous complications.

Case presentation
Here we present a case of a 33-year-old woman, who desired pregnancy, but had a history of primary infertility diagnosed by hysterosalpingography, and endometriosis, which was treated by fulguration and medical management. Concomitantly, the patient was anovulatory. To fulfill her wish, she underwent homologous artificial insemination, after treatment, she successfully conceived quadri-chorionic quadri-amniotic infants, who were born at 37.2 weeks, without perinatal or maternal complications.

Conclusion
This paper presented the parameters of prenatal care, appropriate management approach, and successful resolution without maternal–fetal complications despite the inherent risks of this type of pregnancy.
Consequences of nano and microplastic exposure in rodent models: the known and unknown
Authors: da Silva Brito Walison Augusto , Mutter Fiona , Wende Kristian , Cecchini Alessandra Lourenco , Schmidt Anke , Bekeschus Sander 
Published: April 2022

AbstractThe ubiquitous nature of micro- (MP) and nanoplastics (NP) is a growing environmental concern. However, their potential impact on human health remains unknown. Research increasingly focused on using rodent models to understand the effects of exposure to individual plastic polymers. In vivo data showed critical exposure effects depending on particle size, polymer, shape, charge, concentration, and exposure routes. Those effects included local inflammation, oxidative stress, and metabolic disruption, leading to gastrointestinal toxicity, hepatotoxicity, reproduction disorders, and neurotoxic effects. This review distillates the current knowledge regarding rodent models exposed to MP and NP with different experimental designs assessing biodistribution, bioaccumulation, and biological responses. Rodents exposed to MP and NP showed particle accumulation in several tissues. Critical responses included local inflammation and oxidative stress, leading to microbiota dysbiosis, metabolic, hepatic, and reproductive disorders, and diseases exacerbation. Most studies used MP and NP commercially provided and doses higher than found in environmental exposure. Hence, standardized sampling techniques and improved characterization of environmental MP and NP are needed and may help in toxicity assessments of relevant particle mixtures, filling knowledge gaps in the literature.
Review of a frugal cooling mattress to induce therapeutic hypothermia for treatment of hypoxic-ischaemic encephalopathy in the UK NHS
Authors: Dallera Giulia , Skopec Mark , Battersby Cheryl , Barlow James , Harris Matthew 
Published: April 2022

AbstractHypoxic ischaemic encephalopathy (HIE) is a major cause of neonatal mortality and disability in the United Kingdom (UK) and has significant human and financial costs. Therapeutic hypothermia (TH), which consists of cooling down the newborn’s body temperature, is the current standard of treatment for moderate or severe cases of HIE. Timely initiation of treatment is critical to reduce risk of mortality and disability associated with HIE. Very expensive servo-controlled devices are currently used in high-income settings to induce TH, whereas low-income settings rely on the use of low-tech devices such as water bottles, ice packs or fans. Cooling mattresses made with phase change materials (PCMs) were recently developed as a safe, efficient, and affordable alternative to induce TH in low-income settings. This frugal innovation has the potential to become a reverse innovation for the National Health Service (NHS) by providing a simple, efficient, and cost-saving solution to initiate TH in geographically remote areas of the UK where cooling equipment might not be readily available, ensuring timely initiation of treatment while waiting for neonatal transport to the nearest cooling centre. The adoption of PCM cooling mattresses by the NHS may reduce geographical disparity in the availability of treatment for HIE in the UK, and it could benefit from improvements in coordination across all levels of neonatal care given challenges currently experienced by the NHS in terms of constraints on funding and shortage of staff. Trials evaluating the effectiveness and safety of PCM cooling mattresses in the NHS context are needed in support of the adoption of this frugal innovation. These findings may be relevant to other high-income settings that experience challenges with the provision of TH in geographically remote areas. The use of promising frugal innovations such as PCM cooling mattresses in high-income settings may also contribute to challenge the dominant narrative that often favours innovation from North America and Western Europe, and consequently fight bias against research and development from low-income settings, promoting a more equitable global innovation landscape.
Circulating cell free DNA and citrullinated histone H3 as useful biomarkers of NETosis in endometrial cancer
Authors: Ronchetti Livia , Terrenato Irene , Ferretti Margherita , Corrado Giacomo , Goeman Frauke , Donzelli Sara , Mandoj Chiara , Merola Roberta , Zampa Ashanti , Carosi Mariantonia , Blandino Giovanni , Conti Laura , Lobascio Anna Maria , Iacobelli Marcello , Vizza Enrico , Piaggio Giulia , Gurtner Aymone 
Published: April 2022

Abstract
Background
Cancer mortality is mainly caused by organ failure and thrombotic events. It has been demonstrated that NETosis, a chromatin release mechanism implemented by neutrophils, may contribute to these lethal systemic effects. Our aim was to investigate NETosis biomarkers in endometrial cancer (EC).

Methods
The experiments were conducted on 21 healthy subjects (HS) with no gynecological conditions, and on 63 EC patients. To assess the presence of NETosis features, IHC and IF was performed using antibodies against citrullinated histone H3 (citH3), neutrophil elastase (NE) and histone 2B. Serum levels of cell free DNA (cfDNA), cell free mitochondrial DNA (cfmtDNA) and citH3 were measured by qPCR using one microliter of deactivated serum, and by ELISA assay respectively. Fragmentation pattern of serum cfDNA was analyzed using the Agilent 2100 Bioanalyzer and High Sensitivity DNA Chips. Receiver operating characteristic (ROC) analysis was used to identify a cut off for cfDNA and cfmtDNA values able to discriminate between ECs and HSs. Correlation analysis and multiple correspondence analysis (MCA) between cfDNA, mtcfDNA, citH3 and blood parameters were used to identify the potential association among serum parameters in EC grades.

Results
We demonstrated the presence of NETosis features in tissues from all EC grades. Serum cfDNA and cfmtDNA levels discriminate ECs from HSs and a direct correlation between citH3 and cfDNA content and an inverse correlation between cfmtDNA and citH3 in EC sera was observed, not detectable in HSs. MCA indicates cfDNA, cfmtDNA and citH3 as features associated to G1 and G2 grades. A correlation between increased levels of cfDNA, citH3 and inflammation features was found. Finally, serum nucleosomal cfDNA fragmentation pattern varies in EC sera and correlates with increased levels of cfDNA, citH3, lymphocytes and fibrinogen.

Conclusion
Our data highlight the occurrence of NETosis in EC and indicate serum cfDNA and citH3 as noninvasive biomarkers of tumor-induced systemic effects in endometrial cancer.
Tolvaptan versus fluid restriction in acutely hospitalised patients with moderate-profound hyponatraemia (TVFR-HypoNa): design and implementation of an open-label randomised trial
Authors: Warren Annabelle M. , Grossmann Mathis , Hoermann Rudolf , Zajac Jeffrey D. , Russell Nicholas 
Published: April 2022

Abstract
Background
Current hyponatraemia guidelines are divided on the use of tolvaptan in hospitalised patients with moderate to severe hyponatraemia, due to an uncertain risk-benefit ratio. We will conduct a randomised trial to test the hypothesis that early use of tolvaptan improves the rate of serum sodium correction and clinical outcomes compared with current standard first-line therapy, restriction of fluid intake, without increasing the risk of serum sodium overcorrection.

Methods
We will enrol hospitalised patients with euvolaemic or hypervolaemic hyponatraemia and serum sodium of 115–130 mmol/L at Austin Health, a tertiary care centre in Melbourne, Australia. Participants will be randomised 1:1 to receive either tolvaptan (initial dose 7.5 mg) or fluid restriction (initial limit 1000 ml per 24 h), with titration of therapy based on serum sodium response according to a pre-determined protocol over a 72-h intervention period.
The primary endpoint will be the between-group change in serum sodium over time, from study day 1 to day 4. Secondary endpoints include serum sodium increment in the first 24 and 48 h, proportion of participants with normalised serum sodium, length of hospital stay, requirement for serum sodium re-lowering with intravenous dextrose or desmopressin, cognitive and functional measures (Confusion Assessment Method Short form, Timed Up and Go test, hyponatraemia symptom questionnaire), 30-day readmission rate, treatment satisfaction score and serum sodium 30 days after discharge. The trial will be overseen by an independent Data Safety Monitoring Board. Serum sodium will be monitored every 6–12 h throughout the study period, with pre-specified thresholds for commencing intravenous 5% dextrose if serum sodium rise targets are exceeded.

Discussion
We seek to inform future international guidelines with high-quality data regarding the utility and safety of tolvaptan compared to standard therapy fluid restriction in patients with moderate-severe hyponatraemia in hospital. If tolvaptan use in this patient group is endorsed by our findings, we will have established an evidence-based framework for tolvaptan initiation and monitoring to guide its use.

Trial registration
Australia and New Zealand Clinical Trials Registry ACTRN12619001683123. Registered on December 2 2019
Effectiveness of Tai Chi Yunshou motor imagery training for hemiplegic upper extremity motor function in poststroke patients: study protocol for a randomized clinical trial
Authors: Jiang Lin Hong , Zhao Li Juan , Liu Yang , Zhang Hong , Zhang Si Cong , Cong Wei Qin , Qi Rui 
Published: April 2022

Abstract
Background
Evidence concerning the effect of Tai Chi Yunshou motor imagery training (TCY-MIT) on upper extremity motor function (UE-MF) recovery in poststroke patients is lacking, and few studies have examined the neural mechanisms of MIT. The study was designed to assess the effectiveness of TCY-MIT and its possible neural mechanisms.

Methods/design
The study is an assessor-blinded, parallel, superiority, randomized clinical trial. A total of 78 eligible participants will be randomly assigned to 2 groups in a 1:1 ratio. Participants in the control group will receive (conventional rehabilitation therapies) CRTs for 40 min per day, 6 days per week, for 3 weeks. Participants in the intervention group will receive CRTs combined with TCY-MIT (30 min per day, 6 days per week, for 3 weeks). The primary outcome measure is the Fugl-Meyer Assessment of Upper Extremity. Secondary outcome measures are the Box and Block Test, muscle strength test, modified Barthel index, and Pearson correlation coefficients. All outcomes will be assessed at baseline, after completion of the intervention (1, 2, and 3 weeks), and at the end of follow-up (2 months). The outcome assessor will be blinded to the group allocation of the participants.

Discussion
We expect this assessor-blinded, parallel, superiority, randomized clinical trial to explore the effectiveness of TCY-MIT combined with CRTs compared with CRTs alone for UE-MF in poststroke patients.

Trial registration
Chinese Clinical Trial Registry ID: ChiCTR2100048868. Registered on 19 July 2021
PROmotion of COvid-19 VA(X)ccination in the Emergency Department—PROCOVAXED: study protocol for a cluster randomized controlled trial
Authors: Rodriguez Robert M. , O’Laughlin Kelli , Eucker Stephanie A. , Chang Anna Marie , Rising Kristin L. , Nichol Graham , Pauley Alena , Kanzaria Hemal , Gentsch Alexzandra T. , Li Cindy , Duber Herbie , Butler Jonathan , Eswaran Vidya , Glidden Dave 
Published: April 2022

Abstract
Background
We conducted in-depth interviews to characterize reasons for COVID-19 vaccine hesitancy in emergency department (ED) patients and developed messaging platforms that may address their concerns. In this trial, we seek to determine whether provision of these COVID-19 vaccine messaging platforms in EDs will be associated with greater COVID-19 vaccine acceptance and uptake in unvaccinated ED patients.

Methods
This is a cluster-randomized controlled trial (RCT) evaluating our COVID-19 vaccine messaging platforms in seven hospital EDs (mix of academic, community, and safety-net EDs) in four US cities. Within each study site, we randomized 30 1-week periods to the intervention and 30 1-week periods to the control. Adult patients who have not received a COVID-19 vaccine are eligible with these exclusions: (1) major trauma, intoxication, altered mental status, or critical illness; (2) incarceration; (3) psychiatric chief complaint; and (4) suspicion of acute COVID-19 illness. Participants receive an orally administered Intake survey. During intervention weeks, participants then receive three COVID-19 vaccine messaging platforms (4-min video, one-page informational flyer and a brief, scripted face-to-face message delivered by an ED physician or nurse); patients enrolled during non-intervention weeks do not receive these platforms. Approximately, an hour after intake surveys, participants receive a Vaccine Acceptance survey during which the primary outcome of acceptance of the COVID-19 vaccine in the ED is ascertained. The other primary outcome of receipt of a COVID-19 vaccine within 32 days is ascertained by electronic health record review and phone follow-up. To determine whether provision of vaccine messaging platforms is associated with a 7% increase in vaccine acceptance and uptake, we will need to enroll 1290 patients.

Discussion
Highlighting the difficulties of trial implementation during the COVID-19 pandemic in acute care settings, our novel trial will lay the groundwork for delivery of public health interventions to vulnerable populations whose only health care access occurs in EDs.

Conclusions
Toward addressing vaccine hesitancy in vulnerable populations who seek care in EDs, our cluster-RCT will determine whether implementation of vaccine messaging platforms is associated with greater COVID-19 vaccine acceptance and uptake in unvaccinated ED patients.

Trial status
We began enrollment in December 2021 and expect to continue through 2022.

Trial registration
ClinicalTrials.govNCT05142332. Registered 02 December 2021.