bluuebunny/crossref_metadata_2025_split huggingface dataset:
Killing several birds with one stone: A multi‐indication population pharmacokinetic model and Bayesian estimator for enteric‐coated mycophenolate sodium
Authors: Fromage Yeleen , Sayadi Hamza , Koloskoff Kevin , Marquet Pierre , Labriffe Marc , Monchaud Caroline , Woillard Jean‐Baptiste 
Published: December 2024

AbstractAimsMycophenolic acid (MPA), the active component of enteric‐coated mycophenolate sodium (EC‐MPS), exhibits highly variable pharmacokinetics. Only a few population pharmacokinetic (popPK) models and Bayesian estimators (MAP‐BE) exist for estimating MPA AUC and all in renal transplantation. This study aimed to develop a popPK model and MAP‐BE for MPA AUC estimation using a limited sampling strategy (LSS) in solid organ transplant (SOT), haematopoietic stem cell (HSC) recipients and patients with autoimmune diseases (AID) on EC‐MPS.MethodsFull and sparse MPA pharmacokinetic profiles were extracted from our ISBA system, split into development (75%) and validation (25%) sets. An additional extraction was performed after the modelling process for external validation. Pharmacokinetic parameters were estimated using Monolix® (SAEM algorithm). Several absorption models (first order, transit, gamma) were compared. AUCpredicted by MAP‐BE and LSS was compared to the all‐sample MAP‐BE AUCreference using Simulx®.ResultsWe included 153 PK profiles (863 concentration) from 129 patients (116 SOT and HSC, 13 AID), median [min–max] age 45 years [6–80]. A one‐compartment model with double‐gamma absorption and first‐order elimination best fitted the data. The final model included the EC‐MPS indication and inter‐occasion variability on gamma rate constants. Main PK parameters (mean ± SD) were Cl/F = 4.99 ± 2.22 L/h and Vd/F = 12.60 ± 0.08 L. The optimal LSS at 20 min, 2 h and 4 h post‐dose showed good performance in both validation sets (rMPE −2.67% and −4.91%; RMSE 13.55% and 13.47%).ConclusionsThe double‐gamma absorption model provided an accurate fit. The MAP‐BE offers a tool for EC‐MPS dose individualization in SOT, HSC and AID patients.
Brexucabtagene autoleucel in‐vivo expansion and BTKi refractoriness have a negative influence on progression‐free survival in mantle cell lymphoma: Results from CART‐SIE study
Authors: Stella Federico , Chiappella Annalisa , Magni Martina , Bonifazi Francesca , De Philippis Chiara , Musso Maurizio , Cutini Ilaria , Ljevar Silva , Barbui Anna Maria , Farina Mirko , Martino Massimo , Massaia Massimo , Grillo Giovanni , Angelillo Piera , Botto Barbara , Patriarca Francesca , Krampera Mauro , Arcaini Luca , Tisi Maria Chiara , Zinzani Pierluigi , Sorà Federica , Bramanti Stefania , Pennisi Martina , Carniti Cristiana , Corradini Paolo 
Published: December 2024

SummaryBrexucabtagene autoleucel (brexu‐cel) has revolutionized the treatment of patients affected by mantle cell lymphomas. In this prospective, observational multicentre study, we evaluated 106 patients, with longitudinal brexu‐cel kinetics in peripheral blood monitored in 61 of them. Clinical outcomes and toxicities are consistent with previous real‐world evidence studies. Notably, beyond established poor prognostic factors—such as blastoid variant and elevated lactate dehydrogenase—Bruton tyrosine‐kinase inhibitors (BTKi) refractoriness and platelet count emerged as significant predictors of survival. Specifically, the 1‐year overall survival was 56% in BTKi‐refractory patients compared to 92% in BTKi‐relapsed patients (p = 0.0001). Our study also demonstrated that in‐vivo monitoring of brexu‐cel expansion is feasible and correlates with progression‐free survival and toxicities. Progression‐free survival at 1 year was 74% in patients categorized as strong expanders, based on brexu‐cel peak concentration, versus 54% in poor expanders (p = 0.02). Furthermore, in‐vivo expansion helped identify a high‐risk group of non‐responders, those with progressive or stable disease at the 90‐day post‐infusion evaluation (OR = 4.7, 95% CI = 1.1–34, p = 0.04) characterized by dismal outcomes. When integrated with other clinical factors, monitoring brexu‐cel expansion could assist in recognizing patients at high risk of early relapse.
Optimism and pessimism: a concept for behavioural ecology
Authors: Siewert Viktoria , Kaiser Sylvia , Sachser Norbert , Richter S. Helene 
Published: December 2024

ABSTRACTOriginating from human psychology, the concepts of “optimism” and “pessimism” were transferred to animal welfare science about 20 years ago to study emotional states in non‐human animals. Over time, “optimism” and “pessimism” have developed into valuable welfare indicators, but little focus has been put on the ecological implications of this concept. Here, we aim to bridge this gap and underline the great potential for transferring it to behavioural ecology. We start by outlining why “optimism” and “pessimism” can be considered as aspects of animal personalities. Furthermore, we argue that considering “optimism”/“pessimism” in a behavioural ecology context can facilitate our understanding of individual adjustment to the environment. Specifically, we show how variation in “optimism”/“pessimism” can play a crucial role in adaptation processes to environmental heterogeneity, for example, niche choice and niche conformance. Building on these considerations, we hypothesise that “optimists” might be less plastic than “pessimists” in their behaviour, which could considerably affect the way they adjust to environmental change.
Synthesis and Activity Study of Gefitinib Derivatives Inducing Mitochondrial Apoptosis in Hela Cells
Authors: Li Yue , Hou Xixi , Liu Shujian , Chen Zihao , Wu Qiong , He Baoyu , Guo Jingjing , Wang Lan , Liu Caihong , Mao Long‐Fei 
Published: December 2024

ABSTRACTCervical cancer is the fourth most common cancer among women globally. Its development is closely linked to accelerated cell cycle progression and the inhibition of apoptosis in cervical cancer tissues. Gefitinib has demonstrated efficacy in inhibiting cervical cancer cells, and the 1,2,3‐triazole structure is widely recognized for its role in inducing mitochondrial apoptosis in tumor cells. In this study, we employed click chemistry to modify the structure of gefitinib, leading to the synthesis of 16 derivatives containing the 1,2,3‐triazole moiety. These compounds were evaluated for their in vitro activity against Hela cells. Among them, compound 3p exhibited the most promising anticancer activity, with an IC50 value of 4.09 ± 0.54 μM. Compound 3p significantly inhibited Hela cell colony formation in a dose‐dependent manner, accompanied by noticeable morphological changes. Further investigations revealed that 3p induced apoptosis and caused G2/M phase cell cycle arrest in Hela cells. Western blot analysis showed that 3p increased the Bax/Bcl‐2 ratio and elevated the levels of cleaved caspase‐3 and PARP1, indicating that apoptosis was mediated through the mitochondrial pathway. Additionally, 3p inhibited indoleamine 2,3‐dioxygenase 1 (IDO1) enzymatic activity, and molecular docking studies revealed a strong interaction between 3p and the IDO1 active site, suggesting that IDO1 may be a potential target. In conclusion, compound 3p shows promise as a potential therapeutic agent for cervical cancer.
Frontiers of conservation
Authors: Meinard Yves , Georges Jean‐Yves 
Published: December 2024

AbstractAction‐oriented conservation sciences are crippled by 3 false assumptions. First, although it is recognized in theory that natural and anthropic components of ecosystems are tightly intertwined, in practice, many conservation policies and actions are still based on the assumption that human and nonhuman stakes should be dealt with in deeply different ways. Second, although the anchorage of environmental sciences in values is amply demonstrated, many conservation scientists still assume they will lose their scientific credentials if they actively participate in decision‐making. Finally, although there is much scientific evidence of the permeability—to both protected entities and threats—of static geographic frontiers delimiting protected areas, many conservation policies are still based on the assumption that these frontiers in themselves produce relevant protections. To overcome these false assumptions, it is useful to articulate them in terms of frontiers based on 2 ideas associated with the term. As a synonym of border, frontier materializes a limit whose crossing can have high stakes. As used in phrases such as frontiers of knowledge, the term also refers to the ever‐moving horizon of what should be overcome. These 2 ideas capture the reasons current attempts at overcoming the 3 assumptions remain unsatisfactory. They are also useful for elaborating a new vision of conservation to simultaneously break from the 3 assumptions. Instead of taking fixed geographic frontiers of protected areas for granted, conservation scientists should participate, along with stakeholders and Indigenous peoples, in the collective identification of the conservation problems that need to be addressed. For these problems, decision committees that include representatives of concerned humans and representatives of concerned nonhumans should be formed to determine the temporal and spatial scope of relevant conservation actions. The result would be multidimensional protected areas dynamically fine‐tuned to the conservation issues they address and to changing environmental conditions.
Wolff's theory of consciousness, re‐examined
Authors: Sala Lorenzo 
Published: December 2024

AbstractIn this article, I develop a new account of Wolff's theory of consciousness. In contrast to the received view, I argue that Wolff's texts can be better made sense of by reading ‘perception’ and ‘apperception’ as two radically different acts, each one accounting for radically different aspects of the consciousness of an object and both necessary for its possibility. ‘Perception’ accounts for the intentional component of our representations, that is, for their being about a certain object. Apperception accounts instead for the fact that there is something it is like for us to have a perception of the object in question, without turning the perception in question into one of the intentional objects of consciousness. I also analyse the role played by distinguishing all the other acts that Wolff declares to be necessary for consciousness (attention etc.) and show how they are all necessary for perception to fulfil its role of providing consciousness with its intentional object. On these grounds, I then analyse also Wolff's understanding of self‐consciousness and show how this supports the here proposed reading. Lastly, by comparing their texts, I argue that Wolff's theory of consciousness in his German Metaphysics is fundamentally in line with the one from its Latin counterparts: although in the first the notion of apperception is completely lacking, this does not result into a contrast with the theory from the Latin psychologies, but only in an inferior degree of detail.
Evolutionary View of Liver Pathology
Authors: Dezső Katalin , Paku Sándor , Juhász Mária‐Manuela , Kóbori László , Nagy Péter 
Published: December 2024

ABSTRACTEvolutionary medicine emerged in the late twentieth century, integrating principles of natural selection and adaptation with the health sciences. Today, with a rapidly widening gap between the biology of Homo sapiens and its environment, maladaptation or maladaptive disorders can be detected in almost all diseases, including liver dysfunction. However, in hepatology, as in most medical specialties, evolutionary considerations are neglected because the majority of the medical community is not familiar with evolutionary principles. The aim of this brief review is to highlight an evolutionary approach that may facilitate understanding various liver diseases.
The Spectacularization of NGOs Accountability in Disaster Situations: Evidence From the 2015 Nepal's Earthquakes
Authors: Adhikari Pawan , Upadhaya Bedanand , Adhikari Shovita Dhakal , Aryal Sanjaya , Wijethilake Chaminda 
Published: December 2024

ABSTRACTDrawing on Guy Debord's concept of the spectacle, this article aims to extend our understanding of the way in which certain non‐governmental organizations (NGOs) spectacularize their performance in the context of disaster situations and the continued co‐existence of a multiplicity of accountabilities, with reference to the 2015 Nepal earthquakes. Data for the study were gathered through semi‐structured interviews and document analysis. The findings of the study demonstrate how the voices of many Nepalese NGOs involved in the relief, recovery, and rehabilitation efforts following the 2015 earthquakes remained unheard and how they were forced to compromise their felt responsibilities by having to adhere to the control‐oriented and accounting‐based requirements imposed by the government and funders. Such requirements put certain NGOs, which were established to pursue political and personal goals, in a position to benefit from the situation, allowing them to obfuscate the ground level reality, for instance by manipulating the number of beneficiaries and geographical areas served, showcasing their performance on social media, and facilitating pseudo‐ceremonies and participation. The spectacle created by NGOs was oppressive, exacerbating inequalities in aid distribution and excluding certain groups of beneficiaries from the relief, recovery, and rehabilitation efforts. The key contribution of the study lies in illustrating how both wider society and NGOs’ stakeholders have been relegated to the role of passive spectator–consumers, as they accepted and consumed the NGO‐led representation.
Potential Future Impacts (2016–2055) of Offshore Wind Energy Development on the Atlantic Surfclam, Spisula solidissima, Fishery in the US Mid‐Atlantic Bight Continental Shelf
Authors: Moya Autumn L. , Powell Eric N. , Scheld Andrew M. , Borsetti Sarah , Klinck John M. , Hofmann Eileen E. , Spencer Molly M. , Curchitser Enrique , Munroe Daphne M. 
Published: December 2024

ABSTRACTOffshore wind energy development on the Mid‐Atlantic Bight (MAB) portion of the Northwestern Atlantic continental shelf could have adverse impacts on the future of the Atlantic surfclam, Spisula solidissima, fishery. The current and potential future areas designated for offshore wind energy development overlap with the present‐day and projected Atlantic surfclam fishing grounds and so could limit the fishery. Fishery impacts imposed by displacement of fishing outside wind farm areas and possible restrictions on vessel transit through the wind farms were simulated using a spatially explicit fishery model. The distribution of catch, hours fished, landings per unit effort (LPUE), time at sea, fishing mortality, and the number of fishing trips were projected for five time periods encompassing the period of 2016–2055. Simulations showed a significant decline in the mean of all fishery metrics (apart from LPUE) as the area of wind farm restrictions increased in scale. Impacts were consistently larger when vessel transit through and fishing within offshore wind areas were prohibited. Impacts were also larger for MAB regions off New Jersey and Delmarva than regions farther north and east. These simulations highlight the necessity of evaluating future conditions as warming temperatures shift the surfclam range relative to the immobile wind farm locations. The offshore wind industry must consider projected long‐term impacts of developmental expansion on surrounding sedentary benthic species and the commercially important fisheries that rely on them.
Supported Decision‐Making Interventions in Mental Healthcare: A Systematic Review of Evidence on the Outcomes for People With Mental Ill Health
Authors: Francis Cathy J. , Hazelton Michael , Wilson Rhonda L. 
Published: December 2024

ABSTRACTBackgroundMost people with mental ill health want to be involved in decision‐making about their care, many mental health professionals now recognise the importance of this (at least in‐principle) and the Convention on the Rights of Persons with Disabilities enshrines the ethical imperative to support people in making their own treatment decisions. Nonetheless, there are widespread reports of people with mental ill health being excluded from decision‐making about their treatment in practice.ObjectivesWe conducted a systematic review of quantitative, qualitative and mixed method research on interventions to improve opportunities for the involvement of mental healthcare service users in treatment planning. We sought to consolidate and understand the evidence on the outcomes of shared and supported decision‐making for people with mental ill health.MethodsSeven databases were searched and 5137 articles were screened. Articles were included if they reported on an intervention for adult service users, were published between 2008 and October 2023 and were in English. Evidence in the 140 included articles was synthesised according to the JBI guidance on Mixed Methods Systematic Reviews.ResultsThere was evidence relating to the effects of these interventions on a range of outcomes for people with mental ill health, including on: suicidal crisis, symptoms, recovery, hospital admissions, treatment engagement and on the use of coercion by health professionals. There is favourable evidence for these types of interventions in improving some outcomes for people with mental ill health, more so than treatment‐as‐usual. For other outcomes, the evidence is preliminary but promising. Some areas for caution are also identified.ConclusionsThe review indicates that when the involvement of people with mental ill health in treatment planning is supported, there can be improved outcomes for their health and care. Areas for future research are highlighted.Patient or Public ContributionThis systematic review has been guided at all stages by a researcher with experience of mental health service use, who does not wish to be identified at this point in time. The findings may inform organisations, researchers and practitioners on the benefits of implementing supported decision‐making, for the greater involvement of people with mental ill health in their healthcare.
Review of methodology and re‐analysis of lipidomic data focusing on specialised pro‐resolution lipid mediators (SPMs) in a human model of resolving inflammation
Authors: Homer Natalie Z. M. , Andrew Ruth , Gilroy Derek W. 
Published: December 2024

AbstractUsing a model of UV‐killed E. coli driven dermal inflammation in healthy human volunteers, we originally reported that following inflammatory resolution there was infiltration of macrophages, which, through prostanoids including prostaglandin (PG) E2, imprints long‐term tissue immunity. In addition to the prostanoids, data on levels of Specialised Pro‐Resolution Lipid Mediators (SPMs) throughout inflammatory onset, resolution and post‐resolution phases of this model were presented, but as illustrations rather than as primary data. Therefore, in response to a request for increased transparency, a subset of the original data from our human UV‐killed E. coli model was re‐analysed by two experts from an independent laboratory alongside a review of the methodology used. The prostanoids were detected robustly following re‐analysis but the areas of the chromatographic peaks of the SPM lipid mediators were too small to yield amounts that could be reliably detected and/or quantified using community standards. Importantly, with prostanoids including PGE2 being robustly detected, this re‐analysis does not alter the original report that post‐resolution PGs imprint tissue immunity. Here we show the outcome of this re‐analysis and review the biology surrounding SPMs as a result.
Building the Community Mental Health Nursing Workforce Through a Supported Transition Programme: An Evaluation of a Competency Framework Implementation
Authors: Burkitt Sandra , Hopkins Liza , Olasoji Michael 
Published: December 2024

ABSTRACTThere is a growing focus in the Australian healthcare system of providing mental health care in a community setting. A key feature of the Royal Commission into Victoria's mental health system was to prioritise community‐based care ‘a system with community at its core’. Developing a skilled, flexible and competent nursing workforce is a key objective for any community‐based mental health service as nurses provide a vital role in healthcare delivery. The 3‐year comprehensive nursing qualification has little to no mental health curriculum leaving nursing graduates unprepared for work in mental health, while hospital‐based training for graduate nurses doesn't prepare them for the realities of community‐based work. Significant work in Victoria to develop, refine and implement a competency framework for transition from acute mental health inpatient settings into community‐based services has been undertaken. The aim was to evaluate the effectiveness of this framework in preparing nurses for the community workforce, as well as the barriers and enablers of implementation. A qualitative method investigated experiences of mental health staff who had participated in the transition programme in either aged, adult or a homeless outreach team. Interviews were conducted with transition nurses (n = 5), mentors (n = 4), Clinical managers (n = 3) educators/coordinator (n = 2). The framework structure helped mitigate role stress, allowed for consolidation of theory into practice providing learning opportunities, provided clinical oversight for safe practice, supported autonomous practice, critical thinking, staff wellbeing and demonstrated positive outcomes for consumers and carers. It also had a positive impact on retention and recruitment. Whilst there were limited barriers, the framework implementation relied on organisational support with staff resourcing. Evaluation findings demonstrate the importance of this framework. This structured programme helped facilitate professional development with an integration of knowledge, skills, attitudes and confidence along with staff wellbeing, leading to enhanced clinical practice and outcomes for clients and carers.
Effectiveness of AIMS, a Four‐Week Recovery‐Oriented Suicide Prevention Pathway
Authors: Kar Ray Manaan , Gregory Melanie , Wyder Marianne , Choudhury Md Abu , Geffen Nikki , Lane Abigail , Kinsella Kieran , Lombardo Chiara 
Published: December 2024

ABSTRACTStriking a balance between risk and recovery while supporting people in suicidal distress is a challenging proposition. To address this challenge, a 4‐week AIMS (Assessment, Intervention, Monitoring, Step up/down) pathway was created to support people in suicidal crisis. Each of the four functions was customised into semi‐structured conversations about pain relief. The pathway operationalised tools for relational safety from the PROTECT framework for suicide prevention. To deliver this pathway, a new team was established that included both clinicians and lived experience staff. Scores for the Short Warwick Edinburgh Mental Wellbeing Scale (SWEMWBS) for 300 patients were collected before and after time on the pathway. Paired T tests were performed individually for each item as well as for the total. All 7 items and the total score had statistically significant improvement (p < 0.01). The mean pre‐ and post‐total scores increased from 14.8 to 22.5, strongly indicating clinically meaningful improvement at an individual and group level. The improvement on baseline in each of the seven items ranged from 38% to 73.5%. The top two were in the person's ability to deal with problems and in them feeling relaxed. The study provides a blueprint for collaborative and empowering suicide prevention pathways that strike a balance between positive risk taking and safe care through a relational approach. Professional and lived experience both played a part in capturing hope through evidence‐based person‐centred interventions, helping a person in suicidal crisis improve their mental wellbeing.