bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transactivation of the EGF receptor as a novel desensitization mechanism for G protein-coupled receptors, illustrated by dopamine D2-like and β2 adrenergic receptors
Authors: Kundu Dooti , Min Xiao , Wang Shujie , Peng Lulu , Tian Xinru , Wang Mengling , Kim Kyeong-Man 
Published: October 2024

AbstractTransactivation of epidermal growth factor receptors (EGFR) provides intricate control over multiple regulatory cellular processes that merge the diversity of G protein-coupled receptors (GPCRs) with the robust signaling capacities of receptor tyrosine kinases. Contrary to the typical assertions, our findings demonstrate that EGFR transactivation contributes to the desensitization of GPCRs. Repeated agonist stimulation of certain GPCRs enhanced EGFR transactivation, triggering a series of cellular events associated with GPCR desensitization. This effect was observed in receptors undergoing desensitization (D3R, K149C-D2R, β2AR) but not in those resistant to desensitization (D2R, C147K-D3R, D4R, β2AR mutants lacking GRK2 or GRK6 phosphorylation sites). The EGFR inhibitor AG1478 prevented both desensitization and the associated cellular events. Similarly, these cellular events were also observed when cells were treated with EGF, but only in GPCRs that undergo desensitization. These findings suggest that EGFR transactivation diversifies pathways involved in ERK activation through the EGFR signaling system and also mediates GPCR desensitization. Alongside the widely accepted steric hindrance model, these findings offer new insights into understanding the mechanisms of GPCR desensitization, which occurs through complex cellular processes.
Statistical methods leveraging the hierarchical structure of adverse events for signal detection in clinical trials: a scoping review of the methodological literature
Authors: de Abreu Nunes Laetitia , Hooper Richard , McGettigan Patricia , Phillips Rachel 
Published: October 2024

Abstract
Background
In randomised controlled trials with efficacy-related primary outcomes, adverse events are collected to monitor potential intervention harms. The analysis of adverse event data is challenging, due to the complex nature of the data and the large number of unprespecified outcomes. This is compounded by a lack of guidance on best analysis approaches, resulting in widespread inadequate practices and the use of overly simplistic methods; leading to sub-optimal exploitation of these rich datasets. To address the complexities of adverse events analysis, statistical methods are proposed that leverage existing structures within the data, for instance by considering groupings of adverse events based on biological or clinical relationships.

Methods
We conducted a methodological scoping review of the literature to identify all existing methods using structures within the data to detect signals for adverse reactions in a trial. Embase, MEDLINE, Scopus and Web of Science databases were systematically searched. We reviewed the analysis approaches of each method, extracted methodological characteristics and constructed a narrative summary of the findings.

Results
We identified 18 different methods from 14 sources. These were categorised as either Bayesian approaches (n=11), which flagged events based on posterior estimates of treatment effects, or error controlling procedures (n=7), which flagged events based on adjusted p-values while controlling for some type of error rate. We identified 5 defining methodological characteristics: the type of outcomes considered (e.g. binary outcomes), the nature of the data (e.g. summary data), the timing of the analysis (e.g. final analysis), the restrictions on the events considered (e.g. rare events) and the grouping systems used.

Conclusions
We found a large number of analysis methods that use the group structures of adverse events. Continuous methodological developments in this area highlight the growing awareness that better practices are needed. The use of more adequate analysis methods could help trialists obtain a better picture of the safety-risk profile of an intervention. The results of this review can be used by statisticians to better understand the current methodological landscape and identify suitable methods for data analysis - although further research is needed to determine which methods are best suited and create adequate recommendations.
The development of early warning scores or alerting systems for the prediction of adverse events in psychiatric patients: a scoping review
Authors: Velasquez Valentina Tamayo , Chang Justine , Waddell Andrea 
Published: October 2024

Abstract
Background
Adverse events in psychiatric settings present ongoing challenges for both patients and staff. Despite advances in psychiatric interventions and treatments, research on early warning scores and tools to predict patient deterioration is limited. This review provides a summary of the few tools that have been developed in a psychiatric setting, comparing machine learning (ML) and nonmachine learning/traditional methodologies. The outcomes of interest include the selected key variables that contribute to adverse events and the performance and validation measures of the predictive models.

Methods
Three databases, Ovid MEDLINE, PsycINFO, and Embase, were searched between February 2023 and April 2023 to identify all relevant studies that included a combination of (and were not limited to) the following search terms: "Early warning," "Alerting tool," and "Psychiatry". Peer-reviewed primary research publications were included without imposing any date restrictions. A total of 1,193 studies were screened. A total of 9 studies met the inclusion and exclusion criteria and were included in this review. The PICOS model, the Joanna Briggs Institute (JBI) Reviewer's Manual, and PRISMA guidelines were applied.

Results
This review identified nine studies that developed predictive models for adverse events in psychiatric settings. Encompassing 41,566 participants across studies that used both ML and non-ML algorithmic approaches, performance metrics, primarily AUC ROC, varied among studies between 0.62 and 0.95. The best performing model that had also been validated was the random forest (RF) ML model, with a score of 0.87 and a high sensitivity of 74% and a specificity of 88%.

Conclusion
Currently, few predictive models have been developed for adverse events and patient deterioration in psychiatric settings. The findings of this review suggest that the use of ML and non-ML algorithms show moderate to good performance in predicting adverse events at the hospitals/units where the tool was developed. Understanding these models and the methodology of the studies is crucial for enhancing patient care as well as staff and patient safety research. Further research on the development and implementation of predictive tools in psychiatry should be carried out to assess the feasibility and efficacy of the tool in psychiatric patients.
The relational institution: an ethnographic study of recovery orientation and relational engagement on a psychiatric rehabilitation ward in London
Authors: Whittle Henry J. , Kiely Ed , Millard Isabel , Jadhav Sushrut , Killaspy Helen 
Published: October 2024

Abstract
Background
In the UK, inpatient psychiatric rehabilitation services for complex psychosis aim to provide recovery-orientated treatment to patients, with the goal of supporting sustained stepdown into community living. The extent to which rehabilitation services uphold this recovery orientation is associated with better outcomes. However, few studies have been able to ascertain what promotes or prevents recovery orientation in inpatient settings.

Methods
We conducted an ethnographic study of treatment on a National Health Service (NHS) psychiatric rehabilitation ward in London over six months during August 2022-February 2023. Data were collected through participant observation and semi-structured interviews with 9 patients and 14 staff members. Fieldnotes and interview transcripts were analysed using situational analysis.

Results
Our analysis highlights the importance of what we term ‘relational engagement’ between staff and patients to nurture and sustain recovery-orientated treatment. This relational engagement was embodied through small acts of genuine human connection grounded in mutual acceptance and affective bonding; close attention to detail that communicated curiosity and respect; and recognition, appreciation, and encouragement of the slow and gradual progress that characterises recovery in complex psychosis. Yet, this relational engagement was often limited or foreclosed by the social environment of the ward and the wider institutional context. Limiting elements included the dominance of hospital logics geared towards high-throughput acute treatment and risk management; the presence of audit culture that led to a level of standardisation curtailing more genuine human connection; and staff demoralisation driven by events on and off the ward, including system-wide crises and more localised conflicts and disturbances. Some of these conflicts involved discrimination, most prominently anti-Black racism and homophobia, reflecting wider structural inequalities that characterise inpatient psychiatric populations and the healthcare workforce.

Conclusion
Relationships, often under-prioritised in mental health services, were a key cornerstone of recovery-orientated treatment on a psychiatric rehabilitation ward. The shaping of therapeutic relationships amounted to an active process of relational engagement, which may be afforded or constrained by complex social elements requiring careful consideration in inpatient psychiatry. These social elements go beyond more surface-level factors such as staff training, knowledge, or attitudes and may require structural and system-level interventions.
Creating a safe space: medical students’ perspectives on using actor simulations for learning communication skills
Authors: Antila Asta Kristiina , Lindblom Sari , Louhiala Pekka , Pyörälä Eeva 
Published: October 2024

Abstract
Background
Communication skills are an essential part of clinical competence that need to be acquired during health professions education. Simulations are extensively used for learning communication skills and have long been integral to medical degree programmes. In this research we use qualitative methodology to explore fourth-year medical students’ experiences in simulations aimed at improving versatile doctor-patient communication, focusing on their learning with trained actors.

Methods
The data comprises reflective writings from 208 fourth-year medical students, gathered after a communication skills course. These students provided informed consent for their writings to be included in the research. We performed an inductive qualitative content analysis on the textual data, with findings presented as themes, supported by categories, codes, and excerpts from raw data to enhance the trustworthiness of the analysis.

Results
We identified eight key themes capturing students’ learning experiences through simulations: practising in a safe learning environment, valuing feedback, gaining new perspectives, finding simulations valuable and enjoyable, boosting confidence and self-knowledge, and viewing simulations as authentic and engaging learning opportunities. Some students offered critical perspectives on simulations. Throughout the course, students learned diverse aspects of patient care, emotional and behavioural communication dynamics, and lessons from medical errors. Some students offered critical perspectives on simulations, and a few indicated they did not learn anything new.

Conclusions
A safe learning environment is vital for encouraging learners to explore, make errors, and absorb feedback to improve their communication with patients. Students predominantly valued the communication skills training with actors and the constructive feedback received and given in the debriefing discussions. However, some students expressed critical views toward simulations. Simulations are not static; they evolve and require continual improvements. Hence, we advocate for the ongoing exploration and enhancement of communication skills learning methods, including simulations, with careful consideration for students’ vulnerability and the importance of psychological safety. Additionally, it is critical to address students’ perceptions that certain clinical teachers prioritise biomedical knowledge over communication skills. Providing tailored training for teachers regarding the learning methods and the desired outcomes of communication courses is essential.
Face and content validity of the EMPOWER-UP questionnaire: a generic measure of empowerment in relational decision-making and problem-solving
Authors: Marqvorsen Emilie Haarslev Schröder , Lund Line , Biener Sigrid Normann , Due-Christensen Mette , Husted Gitte R. , Jørgensen Rikke , Mathiesen Anne Sophie , Olesen Mette Linnet , Petersen Morten Aagaard , Pouwer François , Rasmussen Bodil , Rothmann Mette Juel , Thomsen Thordis , Winkley Kirsty , Zoffmann Vibeke 
Published: October 2024

Abstract
Background
Decision-making and problem-solving processes are powerful activities occurring daily across all healthcare settings. Their empowering potential is seldom fully exploited, and they may even be perceived as disempowering. We developed the EMPOWER-UP questionnaire to enable assessment of healthcare users’ perception of empowerment across health conditions, healthcare settings, and healthcare providers’ professional backgrounds. This article reports the initial development of EMPOWER-UP, including face and content validation.

Methods
Four grounded theories explaining barriers and enablers to empowerment in relational decision-making and problem-solving were reviewed to generate a preliminary item pool, which was subsequently reduced using constant comparison. Preliminary items were evaluated for face and content validity using an expert panel of seven researchers and cognitive interviews in Danish and English with 29 adults diagnosed with diabetes, cancer, or schizophrenia.

Results
A preliminary pool of 139 items was reduced to 46. Independent feedback from expert panel members resulted in further item reduction and modifications supporting content validity and strengthening the potential for generic use. Forty-one preliminary items were evaluated through 29 cognitive interviews, resulting in a 36-item draft questionnaire deemed to have good face and content validity and generic potential.

Conclusions
Face and content validation using an expert panel and cognitive interviews resulted in a 36-item draft questionnaire with a potential for evaluating empowerment in user-provider interactions regardless of health conditions, healthcare settings, and healthcare providers’ professional backgrounds.
Identifying factors influencing emerging innovations in hospital discharge decision making in response to system stress: a qualitative study
Authors: Gustavson Allison M. , Miller Matthew J. , Boening Natassia , Hudson Emily M. , Wisdom Jennifer P. , Burke Robert E. , Hagedorn Hildi J. 
Published: October 2024

Abstract
Background
The purpose of this qualitative study was to identify emergent rehabilitation innovations and clinician perceptions influencing their implementation and outcomes related to hospital discharge decision-making during the Coronavirus 2019 pandemic.

Methods
Rehabilitation clinicians were recruited from the Veterans Affairs Health Care System and participated in individual semi-structured interviews guided by the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework. Data were analyzed using a rapid qualitative, deductive team-based approach informed by directed content analysis.

Results
Twenty-three rehabilitation clinicians representing physical (N = 11) and occupational therapy (N = 12) participated in the study. Three primary themes were generated: (1) Innovation: emerging innovations in discharge processes included perceived increases in team collaboration, shifts in caseload prioritization, and alternative options for post-acute care. (2) Recipients: innovations emerged as approaches to communicating discharge recommendations changed (in-person to virtual) and strong patient/family preferences to discharge to the home challenged collaborative goal setting; and (3) Context: the ability of rehabilitation clinicians to innovate and the form of innovations were influenced by the broader hospital system, interdisciplinary team dynamics, and policy fluctuations. Innovations described by participants included (1) use of technological modalities for interdisciplinary collaboration, (2) expansion of telehealth modalities to deliver care in the home, (3) changes in acute care case prioritization, and (4) alternative options for discharge directly to home.

Conclusions
Our findings reinforce that rehabilitation clinicians developed innovative strategies to quickly adapt to multiple systems-level factors that were changing in the face of the COVID-19 pandemic. Future research is needed to assess the impact of innovations, remediate unintended consequences, and evaluate the implementation of promising innovations to respond to emerging healthcare delivery needs more rapidly.
Phase-contrast MRI analysis of cerebral blood and CSF flow dynamic interactions
Authors: Owashi Kimi Piedad , Liu Pan , Metanbou Serge , Capel Cyrille , Balédent Olivier 
Published: October 2024

Abstract
Background
Following the Monro-Kellie doctrine, the Cerebral Blood Volume Changes (CB_VC) should be mirrored by the Cerebrospinal Fluid Volume Changes (CSF_VC) at the spinal canal. Cervical level is often chosen to estimate CB_VC during the cardiac cycle. However, due to the heterogeneity in the anatomy of extracranial internal jugular veins and their high compliance, we hypothesize that the intracranial level could be a better choice to investigate blood and cerebrospinal fluid (CSF) interactions. This study aims to determine which level, intracranial or extracranial, is more suitable for measuring arterial and venous flows to study cerebral blood and CSF dynamics interactions.

Methods
The spinal CSF and cerebral blood flow measured at intracranial and extracranial levels were quantified using cine phase-contrast magnetic resonance imaging (PC-MRI) in 38 healthy young adults. Subsequently, CSF_VC and CB_VC were calculated, and by linear regression analysis (R2 and slope), the relationship between CB_VC at both levels and the spinal CSF_VC was compared. The differences between extracranial and intracranial measurements were assessed using either a paired Student’s t-test or Wilcoxon’s test, depending on the normality of the data distribution.

Results
The CB_VC amplitude was significantly higher at the extracranial level (0.89 ± 0.28 ml/CC) compared to the intracranial level (0.73 ± 0.19 ml/CC; p < 0.001). CSF oscillations through the spinal canal do not completely balance blood volume changes. The R2 and the slope values obtained from the linear regression analysis between CSF and blood flows were significantly higher in magnitude for the intracranial CB_VC (R2: 0.82 ± 0.16; slope: − 0.74 ± 0.19) compared to the extracranial CB_VC (R2: 0.47 ± 0.37; slope: -0.36 ± 0.33; p < 0.001). Interestingly, extracranial CB_VC showed a greater variability compared to intracranial CB_VC.

Conclusion
Our results confirmed that CSF does not completely and instantaneously balance cerebral blood expansion during the cardiac cycle. Nevertheless, the resting volume is very small compared to the total intracranial volume. To our knowledge, this study is the first to demonstrate these findings using cerebral blood flow measured intracranially below the Circle of Willis. Additionally, our findings show that cerebral arterial and venous flow dynamic measurements during the cardiac cycle obtained by PC-MRI at the intracranial plane strongly correlate with CSF oscillations measured in the spinal canal. Therefore, the intracranial vascular plane is more relevant for analyzing cerebral blood and CSF interactions during the cardiac cycle compared to measurements taken at the cervical vascular level.
Metabolic reprogramming and renal fibrosis: what role might Chinese medicine play?
Authors: Wang Weili , Dai Rong , Cheng Meng , Chen Yizhen , Gao Yilin , Hong Xin , Zhang Wei , Wang Yiping , Zhang Lei 
Published: October 2024

AbstractMetabolic reprogramming is a pivotal biological process in which cellular metabolic patterns change to meet the energy demands of increased cell growth and proliferation. In this review, we explore metabolic reprogramming and its impact on fibrotic diseases, providing a detailed overview of the key processes involved in the metabolic reprogramming of renal fibrosis, including fatty acid decomposition and synthesis, glycolysis, and amino acid catabolism. In addition, we report that Chinese medicine ameliorates renal inflammation, oxidative stress, and apoptosis in chronic kidney disease by regulating metabolic processes, thereby inhibiting renal fibrosis. Furthermore, we reveal that multiple targets and signaling pathways contribute to the metabolic regulatory effects of Chinese medicine. In summary, this review aims to elucidate the mechanisms by which Chinese medicine inhibits renal fibrosis through the remodeling of renal cell metabolic processes, with the goal of discovering new therapeutic drugs for treating renal fibrosis.
What is known about patients’ quality of life with Phenylketonuria and their caregivers? A scoping review
Authors: Remor Eduardo , Gabe Kamilla Mueller , Teruya Katia Irie , Doederlein Schwartz Ida Vanessa 
Published: October 2024

Abstract
Background
Phenylketonuria (PKU) is a rare genetic disorder characterized by a deficiency in the metabolism of the essential amino acid phenylalanine, which has a neurotoxic effect at high concentrations. The available treatment for PKU involves limiting the intake of phenylalanine through a restrictive diet. Strict adherence to treatment is essential for a child’s proper development. Owing to their rare and chronic condition, PKU patients and their caregivers need to address many specific challenges, which can affect their quality of life (QoL).

Purpose
This review aimed to identify, characterize, map, and summarize existing knowledge about the quality of life of PKU patients and their primary caregivers.

Methods
A scoping review was conducted following the PRISMA-ScR guidelines. The PubMed, PsycINFO, EMBASE, Scopus, CINAHL, and BVS databases were searched, and articles published between January 2000 and February 2023 were included.

Results
The search resulted in 3249 articles, 29 of which were selected for analysis. Most studies were cross-sectional, and the highest concentration of publications ranged between 2011 and 2021. Generic self-report questionnaires were the tools most commonly used to assess patients’ and their caregivers’ QoL. A significant negative impact on QoL was found in most studies with pediatric patients and caregivers. High current and lifetime blood Phe levels were associated with worse QoL in several domains, and higher tolerance of ingested phenylalanine was associated with a lower impact on QoL. Among caregivers, psychosocial variables such as stress, anxiety, depression, and child behavior problems were associated with poorer QoL. Higher perceived social and emotional support was a protective factor of QoL in caregivers.

Conclusion
Patients of pediatric age and their caregivers, younger caregivers, and female patients and caregivers seem to be especially vulnerable to QoL impairments. The social and emotional dimensions were the most affected. These results emphasize the importance of combining generic and disease-specific assessment tools to achieve a comprehensive assessment. Despite the growing interest in this topic, the longitudinal literature is limited, and there is a lack of interventional studies on this population. Future interventions addressing diet management and providing psychosocial support may benefit the QoL of the PKU population.