bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular events of Bruton's tyrosine kinase inhibitors: A real‐world study based on the United States Food and Drug Administration Adverse Event Reporting System database
Authors: Zhao Zeng‐Xiang , Yang Tian‐Yi , Wang Yuan‐Hui , Zhang Li , Li Ji , Su Yu‐Wen 
Published: June 2024

AimsBruton's tyrosine kinase inhibitors (BTKIs), including first‐generation ibrutinib, second‐generation acalabrutinib and zanubrutinib, may be involved in the mechanisms of action related to adverse events (AEs) of the cardiovascular system. We aimed to characterize the cardiovascular AEs of BTKIs reported in the US Food and Drug Administration (FDA) Adverse Event Reporting System, and to compare the cardiovascular risks of BTKIs.MethodsAcross all indications of three FDA‐approved BTKIs, primary suspect drugs were extracted over two periods: from January 2013 to December 2022 (after the approval of the first BTKI), and from January 2020 to December 2022 (all three BTKIs on the market). Disproportionality was measured by reporting odds ratios (RORs) and information components. Additional analyses were performed without incorporating patients with underlying cardiovascular disease (CVD).ResultsA total of 10 353 cases included the uses of ibrutinib, acalabrutinib and zanubrutinib. Ibrutinib was significantly associated with 47 cardiovascular AEs. Acalabrutinib was associated with new signals, including cardiac failure (ROR = 1.82 [1.13‐2.93]), pulmonary oedema (ROR = 2.15 [1.19‐3.88]), ventricular extrasystoles (ROR = 5.18 [2.15‐12.44]), heart rate irregular (ROR = 3.05 [1.53‐6.11]), angina pectoris (ROR = 3.18 [1.71‐5.91]) and cardiotoxicity (ROR = 25.22 [17.14‐37.10]). In addition, cardiovascular events had an earlier onset in acalabrutinib users. Zanubrutinib was only associated with atrial fibrillation. Acalabrutinib and zanubrutinib had lower ROR values than ibrutinib. The AE signals were generally consistent between the population receiving and not receiving CVD medications.ConclusionsPotential cardiovascular risks identified in this study were not clearly noted on the label of marketed acalabrutinib. Caution should be paid to the cardiovascular risks of BTKIs having been or being developed.
International consensus panel for transurethral resection of bladder tumours metrics: assessment of face and content validity
Authors: Paciotti Marco , Diana Pietro , Gallioli Andrea , De Groote Ruben , Farinha Rui , Ficarra Vincenzo , Gaston Richard , Gontero Paolo , Hurle Rodolfo , Martínez‐Piñeiro Luis , Minervini Andrea , Pansadoro Vito , Van Cleynenbreugel Ben , Wiklund Peter , Casale Paolo , Lughezzani Giovanni , Uleri Alessandro , Mottrie Alexandre , Palou Joan , Gallagher Anthony G. , Breda Alberto , Buffi Nicolò 
Published: June 2024

ObjectiveTo develop performance metrics that objectively define a reference approach to a transurethral resection of bladder tumours (TURBT) procedure, seek consensus on the performance metrics from a group of international experts.MethodsThe characterisation of a reference approach to a TURBT procedure was performed by identifying phases and explicitly defined procedure events (i.e., steps, errors, and critical errors). An international panel of experienced urologists (i.e., Delphi panel) was then assembled to scrutinise the metrics using a modified Delphi process. Based on the panel's feedback, the proposed metrics could be edited, supplemented, or deleted. A voting process was conducted to establish the consensus level on the metrics. Consensus was defined as the panel majority (i.e., >80%) agreeing that the metric definitions were accurate and acceptable. The number of metric units before and after the Delphi meeting were presented.ResultsA core metrics group (i.e., characterisation group) deconstructed the TURBT procedure. The reference case was identified as an elective TURBT on a male patient, diagnosed after full diagnostic evaluation with three or fewer bladder tumours of ≤3 cm. The characterisation group identified six procedure phases, 60 procedure steps, 43 errors, and 40 critical errors. The metrics were presented to the Delphi panel which included 15 experts from six countries. After the Delphi, six procedure phases, 63 procedure steps, 47 errors, and 41 critical errors were identified. The Delphi panel achieved a 100% consensus.ConclusionPerformance metrics to characterise a reference approach to TURBT were developed and an international panel of experts reached 100% consensus on them. This consensus supports their face and content validity. The metrics can now be used for a proficiency‐based progression training curriculum for TURBT.
Positive allosteric modulation of the cannabinoid CB1 receptor potentiates endocannabinoid signalling and changes ERK1/2 phosphorylation kinetics
Authors: Green Hayley M. , Manning Jamie J. , Greig Ian R. , Ross Ruth A. , Finlay David B. , Glass Michelle 
Published: June 2024

AbstractBackground and PurposeActivation of CB1 by exogenous agonists causes adverse effects in vivo. Positive allosteric modulation may offer improved therapeutic potential and a reduced on‐target adverse effect profile compared with orthosteric agonists, due to reduced desensitisation/tolerance, but this has not been directly tested. This study investigated the ability of PAMs/ago‐PAMs to induce receptor regulation pathways, including desensitisation and receptor internalisation.Experimental ApproachBioluminescence resonance energy transfer (BRET) assays in HEK293 cells were performed to investigate G protein dissociation, ERK1/2 phosphorylation and β‐arrestin 2 translocation, while immunocytochemistry was performed to measure internalisation of CB1 in response to the PAMs ZCZ011, GAT229 and ABD1236 alone and in combination with the orthosteric agonists AEA, 2‐AG, and AMB‐FUBINACA.Key ResultsZCZ011, GAT229 and ABD1236 were allosteric agonists in all pathways tested. The ago‐PAM ZCZ011 induced a biphasic ERK1/2 phosphorylation time course compared to transient activation by orthosteric agonists. In combination with 2‐AG but not AEA or AMB‐FUBINACA, ZCZ011 and ABD1236 caused the transient peak of ERK1/2 phosphorylation to become sustained. All PAMs increased the potency and efficacy of AEA‐induced signalling in all pathways tested; however, no notable potentiation of 2‐AG or AMB‐FUBINACA was observed.Conclusion and ImplicationsAgo‐PAMs can potentiate endocannabinoid CB1 agonism by AEA to a larger extent compared with 2‐AG. However, all compounds were found to be allosteric agonists and induce activation of CB1 in the absence of endocannabinoid, including β‐arrestin 2 recruitment and internalisation. Thus, the spatiotemporal signalling of endogenous cannabinoids will not be retained in vivo.
Association between plasma proteome and pulmonary heart disease: A two‐stage Mendelian randomization analysis
Authors: Li Shiyang , Ding Haifeng , Li Qi , Zeng Xiaobin , Zhang Yanyu , Lai Chengyi , Xie Xiaoshuang , Tang Yongjiang , Lan Jianjun 
Published: June 2024

AbstractPulmonary heart disease (PHD) involves altered structure and function of the right ventricle caused by an abnormal respiratory system that causes pulmonary hypertension. However, the association between changes in plasma proteomics and PHD remains unclear. Hence, we aimed to identify causal associations between genetically predicted plasma protein levels and PHD. Mendelian randomization was performed to test the target proteins associated with PHD. Summary statistics for the human plasma proteome and pulmonary heart disease were acquired from the UK Biobank (6038 cases and 426 977 controls) and the FinnGen study (6753 cases and 302 401 controls). Publicly available pQTLs datasets for human plasma proteins were obtained from a largescale genome‐wide association study in the INTERVAL study. The results were validated using a case–control cohort. We first enrolled 3622 plasma proteins with conditionally independent genetic variants; three proteins (histo‐blood group ABO system transferase, activating signal cointegration 1 complex subunit 1, and calcium/calmodulin‐dependent protein kinase I [CAMK1]) were significantly associated with the risk of pulmonary heart disease in the UK Biobank cohort. Only CAMK1 was successfully replicated (odds ratio: 1.1056, 95% confidence interval: 1.019–1.095, p = 0.0029) in the FinnGen population. In addition, the level of CAMK1 in 40 patients with PHD was significantly higher (p = 0.023) than that in the control group. This work proposes that CAMK1 is associated with PHD, underscoring the importance of the calcium signaling pathway in the pathophysiology to improve therapies for PHD.
Utilizing synchronous care to improve cardiovascular and renal health among patients with type 2 diabetes: Proof‐of‐concept results from the DECIDE‐CV clinical programme
Authors: Marques Pedro , Mavrakanas Thomas A. , Guida Julian , Gédéon Tara , Emami Anahita , Alaamiri Abdulkhaliq , Ho Daniel , Possik Elite , Zhang Guang , Tsoukas Michael A. , Sharma Abhinav 
Published: June 2024

AbstractAimThe management of patients with type 2 diabetes is asynchronous, i.e. not coordinated in time, resulting in delayed access to care and low use of guideline‐directed medical therapy (GDMT).MethodsWe retrospectively analysed consecutive patients assessed in the ‘synchronized’ DECIDE‐CV clinic. In this outpatient clinic, patients with type 2 diabetes and cardiovascular or chronic kidney disease are simultaneously assessed by an endocrinologist, cardiologist and nephrologist in the same visit. The primary outcome was use of GDMT before and after the assessment in the clinic, including sodium‐glucose cotransporter 2 inhibitors, glucagon‐like peptide 1 receptor agonists, renin‐angiotensin system blockers and mineralocorticoid receptor antagonists. Secondary outcomes included the baseline‐to‐last‐visit change in surrogate laboratory biomarkers.ResultsThe first 232 patients evaluated in the clinic were included. The mean age was 67 ± 12 years, 69% were men and 92% had diabetes. In total, 73% of patients had atherosclerotic cardiovascular disease, 65% heart failure, 56% chronic kidney disease and 59% had a urinary albumin‐to‐creatinine ratio ≥30 mg/g. There was a significant increase in the use of GDMT:sodium‐glucose cotransporter 2 inhibitors (from 44% to 87% of patients), glucagon‐like peptide 1 receptor agonists (from 8% to 45%), renin‐angiotensin system blockers (from 77% to 91%) and mineralocorticoid receptor antagonists (from 25% to 45%) (p < .01 for all). Among patients with paired laboratory data, glycated haemoglobin, urinary albumin‐to‐creatinine ratio and N‐terminal proB‐type natriuretic peptide levels significantly dropped from baseline (p < .05 for all).ConclusionsJoint assessment of patients with diabetes in a synchronized cardiometabolic clinic holds promise for enhancing GDMT use and has led to significant reductions in surrogate cardiovascular and renal laboratory biomarkers.
Institutionalizing foresight in science, technology, and innovation in sub‐Saharan Africa
Authors: Ouma‐Mugabe John , Botha Anthon , Letaba Petrus 
Published: June 2024

AbstractMotivationForesight is increasingly being institutionalized and used in science, technology and innovation (STI) policy processes around the world. Foresight is a toolbox to help decision‐makers generate intelligence about future scientific and technological advances and to frame long‐term STI policy goals and rationales. Foresight can be used to inform policy to steer research and innovation (R&I) towards attaining sustainable development goals. Yet, foresight is not institutionalized and used in sub‐Saharan Africa (SSA) at a time when many governments are formulating new STI policies and some of their science granting councils (SGCs) are setting R&I priorities.PurposeThis exploratory study is about challenges and opportunities of institutionalizing STI foresight in SSA. It identifies ways of institutionalizing and using STI foresight.Methods and approachA literature review, bibliometric analysis, interviews, an online survey, and focus group discussions were conducted to identify challenges to, and lessons for, institutionalizing STI foresight in SSA. The literature identified good practices for institutionalizing STI foresight in selected developed countries, to draw lessons for SSA.FindingsWhile academic research on STI foresight and related topics is increasing, there is very limited foresight practice in STI policy processes in SSA. This is mainly owing to low awareness of STI foresight, weak technical capacity, and generally a lack of foresight culture in STI policy‐making in the region.Policy implicationsBuilding capacity within governments and establishing a community of practice in STI foresight may help improve the quality and effectiveness of STI policy in SSA. It may enable institutions such as science granting councils (SGCs) to make informed funding decisions, targeting scarce resources at priority research and innovation. Overall, building STI foresight literacy and skills, as well as establishing designated offices for STI foresight, supported by the knowledge to select and adapt foresight tools, will result in improved STI policy‐making in SSA.
To move or not to move: Dispersal of Orius insidiosus in strawberry plants
Authors: Alonso Mariángeles , Guisoni Nara , Rocca Margarita , Greco Nancy 
Published: June 2024

AbstractSpatial and temporal distribution of food resources influences predatory insects' foraging and dispersal behavior. Orius insidiosus (Say) (Hemiptera: Anthocoridae) is a good biological control agent of western flower thrips (WFT), Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae), in the strawberry crop and consumes two‐spotted spider mite (TSSM), Tetranychus urticae Koch (Acari: Tetranychidae), and pollen as well. Augmentative biological control programs may fail if, following release, predators disperse from the crop. We studied the dispersal of O. insidiosus as a function of pollen availability, density of their main prey WFT, and the presence of the alternative prey TSSM, within and between strawberry plants. We found that O. insidiosus remained on the flowers during the 24 h of the assay. The dispersal of predators to a neighboring flower with thrips was approximately six times greater from a flower without pollen than from a flower with pollen. When TSSM was the only prey available, O. insidiosus colonized the leaves, and its dispersal within the plant was greater. At the plot scale, the predator dispersal from the release plant to other plants also depended on the presence of flowering plants and prey. Our results highlight the importance of flowering plants and pollen availability in enhancing the persistence of O. insidiosus in strawberry plants. Releases of this predator in the strawberry crop should be after the beginning of flowering, even at low WFT densities.
Reviewing the impact of hydroxyurea on DNA methylation and its potential clinical implications in sickle cell disease
Authors: Lewis Jasmine , Guilcher Gregory M. T. , Greenway Steven C. 
Published: June 2024

AbstractHydroxyurea (HU) is the most common drug therapy for sickle cell disease (SCD). The clinical benefits of HU derive from its upregulation of fetal hemoglobin (HbF), which reduces aggregation of the mutated sickle hemoglobin protein (HbS) and reduces SCD symptoms and complications. However, some individuals do not respond to HU, or stop responding over time. Unfortunately, current understanding of the mechanism of action of HU is limited, hindering the ability of clinicians to identify those patients who will respond to HU and to optimize treatment for those receiving HU. Given that epigenetic modifications are essential to erythropoiesis and HbF expression, we hypothesize that some effects of HU may be mediated by epigenetic modifications, specifically DNA methylation. However, few studies have investigated this possibility and the effects of HU on DNA methylation remain relatively understudied. In this review, we discuss the evidence linking HU treatment to DNA methylation changes and associated gene expression changes, with an emphasis on studies that were performed in individuals with SCD. Overall, although HU can affect DNA methylation, research on these changes and their clinical effects remains limited. Further study is likely to contribute to our understanding of hematopoiesis and benefit patients suffering from SCD.
Early effect of onabotulinumtoxinA on EEG‐based functional connectivity in patients with chronic migraine: A pilot study
Authors: Conti Matteo , Bovenzi Roberta , Palmieri Maria Giuseppina , Placidi Fabio , Stefani Alessandro , Mercuri Nicola Biagio , Albanese Maria 
Published: June 2024

AbstractObjectiveIn this pilot prospective cohort study, we aimed to evaluate, using high‐density electroencephalography (HD‐EEG), the longitudinal changes in functional connectivity (FC) in patients with chronic migraine (CM) treated with onabotulinumtoxinA (OBTA).BackgroundOBTA is a treatment for CM. Several studies have shown the modulatory action of OBTA on the central nervous system; however, research on migraine is limited.MethodsThis study was conducted at the Neurology Unit of “Policlinico Tor Vergata,” Rome, Italy, and included 12 adult patients with CM treated with OBTA and 15 healthy controls (HC). Patients underwent clinical scales at enrollment (T0) and 3 months (T1) from the start of treatment. HD‐EEG was recorded using a 64‐channel system in patients with CM at T0 and T1. A source reconstruction method was used to identify brain activity. FC in δ‐θ‐α‐β‐low‐γ bands was analyzed using the weighted phase‐lag index. FC changes between HCs and CM at T0 and T1 were assessed using cross‐validation methods to estimate the results’ reliability.ResultsCompared to HCs at T0, patients with CM showed hyperconnected networks in δ (p = 0.046, area under the receiver operating characteristic curve [AUC: 0.76‐0.98], Cohen's κ [0.65‐0.93]) and β (p = 0.031, AUC [0.68‐0.95], Cohen's κ [0.51‐0.84]), mainly involving orbitofrontal, occipital, temporal pole and orbitofrontal, superior temporal, occipital, cingulate areas, and hypoconnected networks in α band (p = 0.029, AUC [0.80‐0.99], Cohen's κ [0.42‐0.77]), predominantly involving cingulate, temporal pole, and precuneus. Patients with CM at T1, compared to T0, showed hypoconnected networks in δ band (p = 0.032, AUC [0.73‐0.99], Cohen's κ [0.53‐0.90]) and hyperconnected networks in α band (p = 0.048, AUC [0.58‐0.93], Cohen's κ [0.37‐0.78]), involving the sensorimotor, orbitofrontal, cingulate, and temporal cortex.ConclusionThese preliminary results showed that patients with CM presented disrupted EEG‐FC compared to controls restored by a single session of OBTA treatment, suggesting a primary central modulatory action of OBTA.
Hard to reach? Methodological challenges researching vulnerable, gang‐involved, young people
Authors: Barker Rhiannon , Bonell Chris , Melendez‐Torres G. J. 
Published: June 2024

AbstractIntroductionResearch with young people (YP) is ethically challenging and bound in a complex maze of issues relating to power, voice and representation. Such sensitivities mean that the challenges raised in researching marginalised YP are often hard to navigate. This paper reports on research carried out with YP to explore links between mental health, school exclusion and involvement in criminal gangs. It aims to provide a practical guide to negotiating some of the methodological and ethical challenges experienced.MethodIn‐depth interviews conducted with 28 YP (aged 14–24 years) who were gang involved or seen to be at risk of gang involvement. Research was conducted in youth clubs, alternative provision and youth justice settings.Results: Observations/ReflectionsWe reflect on how navigating ethics can create barriers to involving YP as primary informants in research. We consider why it is important to overcome these hurdles and how public engagement work with recognised gatekeepers and the use of creative interview methods can facilitate meaningful encounters, where YP feel able to share valuable insights into their lives.ConclusionAlongside a number of specific learning points, the paper reflects on theories behind research with YP, including the need for recognition of power imbalances and reflexivity. It concludes with thoughts on the practical realities of achieving meaningful participation or an ‘authentic voice’ with marginalised groups and the importance of this in informing policy and practice.Patient or Public ContributionThe focus of this work was to collect experiences of YP who are recognised as gang‐involved or at risk of being so, with a view to informing health and education policies. The scoping study for the project involved extensive public engagement work with YP exploring and trialling suitable methods of accessing, recruiting and ultimately interviewing this target group. This is central to the discussion within the body of the paper.
A systematic review on the impact of sub‐epidermal moisture assessments on pressure ulcer/injury care delivery pathways
Authors: Avsar Pinar , Patton Declan , Cuddigan Janet , Moore Zena 
Published: June 2024

AbstractTo assess all published studies which describe what happens to the delivery of pressure ulcer/injury (PI/PU) care pathways as a result of detecting raised sub‐epidermal moisture (SEM) delta (∆ ≥ 0.6). We undertook a systematic review of the literature, and included original research studies using either a prospective or retrospective study design that report the impact that assessment using SEM assessments have on healthcare practitioners' delivery of PI/PU care pathways in adults at risk of developing PI/PUs. The review protocol was registered on PROSPERO (CRD42023416975). A literature search was conducted in May 2023, using PubMed, CINAHL, Scopus, Cochrane, EMBASE, Web of Science and Science Direct databases. Data were extracted using a data extraction tool including elements such as country, setting, sample size, intervention, control and quality appraisal was undertaken using the Evidence‐based Librarianship. We identified nine papers published between 2017 and 2022. The majority of these studies were conducted in England (n = 6; 67%). The systematic review included studies conducted across multiple care settings including acute care, medical‐surgical units, and palliative care, highlighting the importance of PI/PU prevention and management across diverse patient populations. The PI/PU care pathways implemented in the studies varied, but commonly included elements such as the application or increased use of pressure‐redistributing mattresses/cushions, implementation of repositioning plans, management of incontinence and moisture, regular skin inspection, and assessment of patient mobility. Out of the nine studies identified, seven reported PI/PU incidence. A meta‐analysis of seven studies (N = 18 451) demonstrated a statistically significant reduction in visual PI/PU development in favour of SEM‐guided care pathways compared to usual care (the odds ratio = 0.36 [95% confidence interval: 0.24–0.53, p < 0.00001]). This systematic review provides evidence that implementing SEM assessments in patients at risk of developing PI/PUs prompts anatomy‐specific clinical actions. The subsequent implementation of enhanced and targeted skin care interventions leads to consistent and sustained reductions in hospital‐acquired PU incidence. The findings emphasise the importance of incorporating SEM assessments as part of comprehensive PI/PU prevention strategies in all care settings and patient populations. This systematic review is limited by the predominance of observational studies and variable study quality. Future research should focus on randomised trials in different care settings that monitor the efficacy of preventive interventions and their impact in reducing PI/PU incidence when implemented based on SEM assessments.