bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined Inhibition of EZH2 and FGFR is Synergistic in BAP1-deficient Malignant Mesothelioma
Authors: Badhai Jitendra , Landman Nick , Pandey Gaurav Kumar , Song Ji-Ying , Hulsman Danielle , Krijgsman Oscar , Chandrasekaran Gayathri , Berns Anton , van Lohuizen Maarten 
Published: December 2023

Abstract

Malignant mesothelioma is a highly aggressive tumor with a survival of only 4–18 months after diagnosis. Treatment options for this disease are limited. Immune checkpoint blockade using ipilimumab and nivolumab has recently been approved as a frontline therapy, but this led to only a small improvement in overall patient survival. As more than half of patients with mesothelioma have alterations in the gene encoding for BAP1 this could be a potential marker for targeted therapies. In this study, we investigated the synergistic potential of combining EZH2 inhibition together with FGFR inhibition for treatment of BAP1-deficient malignancies. The efficacy of the combination was evaluated using human and murine preclinical models of mesothelioma and uveal melanoma in vitro. The efficacy of the combination was further validated in vivo by using BAP1-deficient mesothelioma xenografts and autochthonous mouse models. In vitro data showed sensitivity to the combined inhibition in BAP1-deficient mesothelioma and uveal melanoma tumor cell lines but not for BAP1-proficient subtypes. In vivo data showed susceptibility to the combination of BAP1-deficient xenografts and demonstrated an increase of survival in autochthonous models of mesothelioma. These results highlight the potential of this novel drug combination for the treatment of mesothelioma using BAP1 as a biomarker. Given these encouraging preclinical results, it will be important to clinically explore dual EZH2/FGFR inhibition in patients with BAP1-deficient malignant mesothelioma and justify further exploration in other BAP1 loss–associated tumors.

Significance:
Despite the recent approval of immunotherapy, malignant mesothelioma has limited treatment options and poor prognosis. Here, we observe that EZH2 inhibitors dramatically enhance the efficacy of FGFR inhibition, sensitising BAP1-mutant mesothelioma and uveal melanoma cells. The striking synergy of EZH2 and FGFR inhibition supports clinical investigations for BAP1-mutant tumors.
Comparison of Stress-Rest and Stress-LGE Analysis Strategy in Patients Undergoing Stress Perfusion Cardiovascular Magnetic Resonance
Authors: Swoboda Peter P. , Matthews Gareth D.K. , Garg Pankaj , Plein Sven , Greenwood John P. 
Published: December 2023

BACKGROUND:
Stress perfusion cardiovascular magnetic resonance can be performed without rest perfusion for the quantification of ischemia burden. However, the optimal method of analysis is uncertain.

METHODS:
We identified 666 patients from CE-MARC (Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease) with complete stress perfusion, rest perfusion, late gadolinium enhancement (LGE), and quantitative coronary angiography data. For each segment of the 16-segment model, perfusion was visually graded during stress and rest imaging, with infarct transmurality assessed from LGE imaging. In the stress-LGE analysis, a segment was defined as ischemic if it had a subendocardial perfusion defect with no infarction. Rest perfusion was not used in this analysis. We compared the diagnostic accuracy of stress-LGE analysis against quantitative coronary angiography and the stress-rest method validated in the original CE-MARC analysis. The diagnostic accuracy of the stress-LGE method was evaluated with different thresholds of infarct transmurality used to define whether an infarcted segment had peri-infarct ischemia.

RESULTS:

The optimal stress-LGE analysis classified all segments with a stress perfusion defect as ischemic unless they had >75% infarct transmurality (area under the curve, 0.843; sensitivity, 75.6%; specificity, 93.1%;
P
<0.001). This analysis method has superior diagnostic accuracy to the stress-rest method (area under the curve, 0.834; sensitivity, 73.6%; specificity, 93.1%;
P
<0.001,
P
value for difference=0.02). Patients were followed-up for median 6.5 years for major adverse cardiovascular events, with the presence of inducible ischemia by either the stress-LGE or stress-rest analysis being similar and strongly predictive (hazard ratio, 2.65;
P
<0.001, for both).

CONCLUSIONS:
In this analysis of CE-MARC, the optimum definition of inducible ischemia was the presence of a stress-induced perfusion defect without transmural infarction. This definition improved the diagnostic accuracy compared with the stress-rest analysis validated in the original study. The absence of ischemia by either analysis strategy conferred a favorable long-term prognosis.
Prevalence and correlates of psychological distress among national community-based adult populations in Nauru, Tukelau and Tuvalu
Authors: Pengpid Supa , Peltzer Karl 
Published: December 2023

Aims: The aim of the study was to estimate the prevalence and correlates of psychological distress (PD) in three small Pacific Island countries. Method: National cross-sectional data (pooled sample N = 3,088, 18–69 years) of participants from the STEPS surveys in Nauru (2015/16; N = 1382), Tukelau (2014; N = 554) and Tuvalu (2015; N = 1152) were analysed. Results: In the pooled sample 30.4% participants had PD (⩾20 scores), 18.1% mild (20–24 scores), 7.8% moderate (25–29 scores) and 4.4% severe (30–50 scores) PD. The prevalence of PD in Nauru was 41.5%, in Tukelau 5.0% and in Tuvalu 22.7%. In the adjusted logistic regression analysis with the pooled sample, younger age (18–39 years), alcohol family problems, heart attack/stroke, current smoking, high salt intake and high sedentary behaviour were positively associated with PD, while male sex and being from Tukelau and Tuvalu were negatively associated with PD. Conclusion: Almost one in three participants reported PD and several associated factors were found that can be targeted in population interventions.
A systematic practice review: Providing palliative care for people with Parkinson’s disease and their caregivers
Authors: Garon Michela , Weck Christiane , Rosqvist Kristina , Odin Per , Schrag Anette , Krikmann Ülle , Pedrosa David J , Antonini Angelo , Lorenzl Stefan , Martins Pereira Sandra , Paal Piret 
Published: December 2023

Background: People with Parkinson’s disease has significant and increasing physical, psychosocial and spiritual needs, as well as problems with coordination and continuity of care. Despite the benefits that palliative care could offer, there is no consensus on how it should be delivered. Aim: The aim of this study is to provide a pragmatic overview of the evidence to make clinical recommendations to improve palliative care for people with Parkinson’s disease and their caregivers. Design: A systematic review method was adopted to determine the strength of evidence, supported by feedback from an expert panel, to generate the ‘do’, ‘do not do’ and ‘do not know’ recommendations for palliative care. Data sources: Searches were conducted via OVID to access CINAHL, MEDLINE, EMBASE and the Cochrane Library from 01/01/2006 to 31/05/2021. An additional search was conducted in December 2022. The search was limited to articles that included empirical studies of approaches to enabling palliative care. Results: A total of 62 studies met inclusion criteria. There is evidence that education about palliative care and movement disorders is essential. palliative care should be multi-disciplinary, individualised and coordinated. Proactive involvement and support of caregivers throughout the illness is recommended. Limited data provide referral indicators for palliative care integration. Discussions about advance care planning should be held early. Conclusions: Consideration of palliative care integration based on symptom burden and personal preferences, coordination and continuity of care are needed to maintain the quality of life of people with Parkinson’s disease and their caregivers.
Parents’ experiences of being involved in medical decision-making for their child with a life-limiting condition: A systematic review with narrative synthesis
Authors: Polakova Kristyna , Ahmed Faraz , Vlckova Karolina , Brearley Sarah G 
Published: December 2023

Background: Parental involvement in the decision-making processes about medical treatment for children with life-limiting conditions is recognised as good practice. Previous research highlighted factors affecting the decision-making process, but little is known about how parents experience their participation. Aim: To explore how parents experience their participation in the process of decision-making about treatment and future care for their children with life-limiting conditions. Design: A systematically constructed review using narrative synthesis. The PRISMA guidelines were followed to report the findings. Databases Medline, EMBASE, SCOPUS, CINAHL and PsycINFO were searched up to December 2023. The study protocol was registered at PROSPERO (RN CRD42021215863). Results: From the initial 2512 citations identified, 28 papers met the inclusion criteria and were included in the review. A wide range of medical decisions was identified; stopping general or life-sustaining treatment was most frequent. Narrative synthesis revealed six themes: (1) Temporal aspects affecting the experience with decision-making; (2) Losing control of the situation; (3) Transferring the power to decide to doctors; (4) To be a ‘good’ parent and protect the child; (5) The emotional state of parents and (6) Sources of support to alleviate the parental experience. Conclusions: Parental experiences with decision-making are complex and multifactorial. Parents’ ability to effectively participate in the process is limited, as they are not empowered to do so and the circumstances in which the decisions are taking place are challenging. Healthcare professionals need to support parental involvement in an effective way instead of just formally asking them to participate.
Inter-institutional analysis of the outcome after postcardiotomy veno-arterial extracorporeal membrane oxygenation
Authors: Biancari Fausto , Mäkikallio Timo , Loforte Antonio , Kaserer Alexander , Ruggieri Vito G , Cho Sung-Min , Kang Jin Kook , Dalén Magnus , Welp Henryk , Jónsson Kristján , Ragnarsson Sigurdur , Hernández Pérez Francisco J , Gatti Giuseppe , Alkhamees Khalid , Fiore Antonio , Lechiancole Andrea , Rosato Stefano , Spadaccio Cristiano , Pettinari Matteo , Perrotti Andrea , Sahli Sebastian D , L’Acqua Camilla , Arafat Amr A , Albabtain Monirah A , AlBarak Mohammed M , Laimoud Mohamed , Djordjevic Ilija , Krasivskyi Ihor , Samalavicius Robertas , Jankuviene Agne , Alonso-Fernandez-Gatta Marta , Wilhelm Markus J , Juvonen Tatu , Mariscalco Giovanni 
Published: December 2023

Introduction: Patients requiring postcardiotomy veno-arterial extracorporeal membrane oxygenation (V-A-ECMO) have a high risk of early mortality. In this analysis, we evaluated whether any interinstitutional difference exists in the results of postcardiotomy V-A-ECMO. Methods: Studies on postcardiotomy V-A-ECMO were identified through a systematic review for individual patient data (IPD) meta-analysis. Analysis of interinstitutional results was performed using direct standardization, estimation of observed/expected in-hospital mortality ratio and propensity score matching. Results: Systematic review of the literature yielded 31 studies. Data from 10 studies on 1269 patients treated at 25 hospitals were available for the present analysis. In-hospital mortality was 66.7%. The relative risk of in-hospital mortality was significantly higher in six hospitals. Observed versus expected in-hospital mortality ratio showed that four hospitals were outliers with significantly increased mortality rates, and one hospital had significantly lower in-hospital mortality rate. Participating hospitals were classified as underperforming and overperforming hospitals if their observed/expected in-hospital mortality was higher or lower than 1.0, respectively. Among 395 propensity score matched pairs, the overperforming hospitals had significantly lower in-hospital mortality (60.3% vs 71.4%, p = 0.001) than underperforming hospitals. Low annual volume of postcardiotomy V-A-ECMO tended to be predictive of poor outcome only when adjusted for patients’ risk profile. Conclusions: In-hospital mortality after postcardiotomy V-A-ECMO differed significantly between participating hospitals. These findings suggest that in many centers there is room for improvement of the results of postcardiotomy V-A-ECMO.
Development and evaluation of a risk score model based on a WNT score gene-associated signature for predicting the clinical outcome and the tumour microenvironment of hepatocellular carcinoma
Authors: Li Penghui , Ma Xiao , Huang Di , Gu Xinyu 
Published: December 2023

Background: Hepatocellular carcinoma (HCC) is currently one of the most life-threatening diseases worldwide. However, the factors, genes, and processes involved in the mechanisms of HCC initiation, development, and metastasis remain to be identified. Methods: WNT signalling pathways may play important roles in cancer initiation and progression. Thus, it would be informative to construct a WNT signature-based gene model for the prognosis of HCC and the prediction of therapeutic efficacy. We curated genomic profiles for HCC from The Cancer Genome Atlas (TCGA) and divided them into training and internal validation datasets. We also used samples from GSE14520 and HCCDB18 as validation datasets and clustered them by ConsensusClusterPlus analysis. We applied WebGestaltR to the WNT score-associated differentially expressed genes (DEGs) and conducted a signalling pathway enrichment analysis. We assessed the tumour immune microenvironment with ESTIMATE, Microenvironment Cell Populations (MCP)-counter, single-sample gene set enrichment analysis (ssGSEA), and tumour immune dysfunction and exclusion (TIDE). Results: We performed a least absolute shrinkage and selection operator (LASSO) regression analysis to identify the prognosis-related hub genes, identified the risk and protective factor genes associated with HCC, classified them into two clusters, and found that Cluster 2 had a significantly better prognosis than Cluster 1. Moreover, the latter had advanced clinical features compared with the former. Uridine-cytosine kinase 1 (UCK1), myristoylated alanine-rich C-kinase substrate-like protein 1 (MARCKSL1), P-antigen family member 1 (PAGE1), and killer cell lectin-like receptor B1 (KLRB1) were detected and used to construct a simplified prognostic model for HCC. The high risk score subgroup showed a poorer prognosis than the low risk score subgroup, and the model assessed HCC prognosis consistently and effectively. Conclusions: The WNT score-related gene-based model designed and evaluated herein had strong prognostic and predictive ability for HCC and could, therefore, facilitate decision-making in the prognosis and therapeutic efficacy assessment of HCC.
Multiple, active-offer referrals for HIV pre-exposure prophylaxis by nurses yields high uptake among gay, bisexual, and other men who have sex with men
Authors: Orser Lauren , O’Byrne Patrick 
Published: December 2023

Introduction Current Canadian guidelines focus on indications and uptake of preexposure prophylaxis (PrEP) among groups at-risk for HIV, such as gay, bisexual, and men who have sex with men (GBM). Less, however, is known about the outcomes of PrEP offers. This study presents on the responses of GBM to multiple offers for PrEP. Methods In Ottawa, Canada, we instituted Canada’s first nurse-led PrEP program, pre-exposure prophylaxis by nurses (PrEP-RN), where nurses offered PrEP referrals to persons with indicators for HIV. Responses to offers from nurses and HIV diagnoses were recorded and assessed for multiple occurrences based on responses. Descriptive analyses were used to report frequencies and percentages of findings and chi-square analyses were conducted to determine significance based on HIV risk for those who accepted versus declined PrEP Results Over a 4-year period, 644 PrEP offers were made to 236 unique patients, all of whom were GMB, the majority of whom identified as male. Of the eligible patients, 50.8% accepted and 50.0% declined after multiple offers. Seven trajectories were identified in terms of reasons for accepting or declining PrEP. PrEP referrals made based on clinical guidelines and to those who had changes in risk factors over time were significantly correlated with PrEP acceptance. We noted five HIV diagnoses, all of which were among GBM who declined PrEP at least once. Conclusions Based on these findings, it appears multiple PrEP may yield increased PrEP acceptance among a sample of GBM.
The Incidence of Torsades de Pointes With Perioperative Triple Antiemetic Administration
Authors: Nuttall Gregory A. , Reed Alyssa M. , Pham (Louis) Khue D. , Oyen Lance J. , Marsland Samuel P. , Ackerman Michael J. 
Published: December 2023

Background: The safety of triple antiemetic therapy consisting of ondansetron, haloperidol, and a steroid, to surgical patients is unknown. Objective: To determine the incidence of torsade de pointes (TdP) or death following perioperative administration of triple antiemetic therapy. Methods: A retrospective cohort study identified 19,874 patients who received 22,202 doses of triple antiemetics during the 2.5-year time frame from March 4, 2020 to September 7, 2022 for surgical nausea prophylaxis or treatment of nausea. These patients above were cross-matched with an electrocardiogram and adverse outcome database; this identified 226 patients with documentation of a QTc > 450 ms, all ventricular tachycardias including TdP within 48 hours of receiving triple antiemetic therapy, or death within 7 days of receiving ondansetron. Results: There were 3 patients who had documented VT (n = 3), but there were no documented incidents of TdP (n = 0). There were 9 codes called on patients within 48 hours of medication administration, and none of them were due to ventricular arrythmias (n = 0). A total of 11 patients died within 7 days of triple antiemetic therapy. Ten of the 11 deaths were determined to not be from the triple antiemetic. One patient died at home within 24 hours of the procedure of an unknown cause (n = 1). Conclusions and Relevance: No episodes of TdP were identified in patients receiving triple antiemetic therapy perioperatively, though the cause of death in 1 patient could not be determined. This suggest that low-dose triple antiemetic therapy is low risk for the development of TdP.
Angioplasty for dysfunctional arteriovenous fistulas: A meta-analysis of recent randomized controlled trials compared paclitaxel-coated balloon versus conventional balloon angioplasty
Authors: Yang Qin , Xia Congying 
Published: December 2023

Background: Stenosis in arteriovenous fistulas (AVF) due to neointimal hyperplasia is one of the most common causes of hemodialysis vascular access dysfunction. Treating patients with dysfunctional AVF with drug-coated balloon (DCB) angioplasty may potentially improve outcomes. Objectives: This systematic review aimed to compare the effectiveness and safety of DCB angioplasty versus conventional balloon angioplasty by pooling evidence from the most recent randomized controlled trials. Methods: We conducted a comprehensive literature search in the Web of Science, Embase, and Cochrane central databases. Two independent researchers screened the article, extracted interest, and evaluated included studies for risk of bias. Pooled estimation was conducted in terms of 6-month target-lesion primary patency (TLPP) and target-lesion reintervention (TLR), as well as other outcomes. Results: Results were expressed with odds ratio (OR) and 95% confidence interval (CI). A total of five RCTs were identified and included in the meta-analyses, with 1107 participants. DCB has a trend of a higher rate of TLPP (OR 1.79, 95% CI 0.66–4.90, p = 0.181) and a significantly lower rate of TLR (0.52, 95% CI 0.29–0.92, p = 0.034), as compared to conventional balloon angioplasty. No difference in the 6-month access circuit primary patency and reinvention was observed between the two groups. Conclusion: DCB may be an alternative treatment of dysfunctional AVF given a trend of a higher rate of TLPP and a significantly lower rate of TLR than conventional balloon angioplasty within 6 months after the indexed procedure. Moreover, DCB was non-inferior to conventional balloon angioplasty in terms of safety. Considering variations in the DCB technique, further studies are warranted for a standardized process.
Early arteriovenous fistula failure associated with mortality and major adverse cardiovascular events in patients undergoing incident hemodialysis
Authors: Okubo Aiko , Doi Toshiki , Yamada Yumi , Morii Kenichi , Nishizawa Yoshiko , Yamashita Kazuomi , Fudaba Yasuhiro , Shigemoto Kenichiro , Mizuiri Sonoo , Usui Koji , Arita Michiko , Naito Takayuki , Masaki Takao 
Published: December 2023

Background: Arteriovenous fistula (AVF) patency is important for patients undergoing hemodialysis. The association between early AVF failure and the prognosis, including all-cause mortality and major adverse cardiovascular events (MACE), has not been fully investigated. The present study was performed to investigate the association between early AVF failure and 3-year mortality, cardiovascular disease (CVD) mortality, and MACE. Methods: We analyzed 358 patients who started hemodialysis in our institution from October 2008 to February 2020. We defined early AVF failure as cases requiring percutaneous transluminal angioplasty or reoperation within 1 year after AVF surgery. The patients were divided into two groups according to the presence or absence of early AVF failure, and the prognosis of each group was examined. The association between early AVF failure and outcomes (3-year all-cause mortality, CVD mortality, and MACE) was determined using Cox proportional hazards regression analysis. Results: During the 3-year follow-up, 75 (20.9%) patients died (cardiovascular death: n = 39) and 145 patients developed MACE. According to the multivariable analysis, the early AVF failure group had a significantly higher risk of 3-year all-cause mortality (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.09–1.83; p = 0.009), CVD mortality (HR, 1.54; 95% CI, 1.29–2.08; p < 0.001), and MACE (HR, 1.68; 95% CI, 1.25–2.26; p < 0.001). When the patients were stratified by age, early AVF failure was associated with 3-year all-cause mortality in all groups except for the younger group (<65 years of age). Conclusions: Early AVF failure was associated with an increased risk of 3-year all-cause mortality, CVD mortality, and MACE.