bluuebunny/crossref_metadata_2025_split huggingface dataset:
UK paediatric clinical trial protocols: A review of guidance for participant management and care in the event of premature termination
Authors: Pluess-Hall Helen , Smith Paula , Menzies Julie 
Published: November 2024

Background/Aims: Clinical trials provide an opportunity to identify new treatments and can offer patients access to treatments otherwise unavailable. However, approximately 10% of paediatric clinical trials discontinue before the trial has completed. If this premature termination is because the trial treatment(s) being investigated are identified to be ineffective or unsafe, it results in the abrupt discontinuation of the investigational medicinal product for participants. For some participants, there may not be other treatment options to pursue at the trial-end. Trials prematurely terminating can be a distressing experience for all involved and currently there is little published evidence about the guidance provided to healthcare professionals in the event of premature trial termination. The study protocol is the source of guidance for healthcare professionals delivering clinical research, detailing how to conduct all aspects of the trial. The aim was to quantify the proportion of clinical trial protocols that included premature trial termination and subsequently those that provided instructions related to participant management and care. In addition, to analyse the context in which premature termination was included and the detail of any instructions for participant management and care. Methods: The ClinicalTrials.gov database was searched by a single reviewer for UK interventional drug trials enrolling children with an available study protocol. Protocols were searched to assess if the risk of premature trial termination was identified, the context for premature termination being included, if information was provided to support the management and care of participants should this situation occur and the detail of those instructions. Data were summarised descriptively. Results: Of 245 clinical trial protocols, 235 (95.9%) identified the possibility of premature trial termination, the majority within the context of the sponsor asserting their right to terminate the trial (82.7%, 115/235) and providing reasons why the trial could be stopped (65.5%, 91/235). Forty-two percent (98/235) provided guidance for participant management and care, most commonly to contact/inform the participant (45.9%, 45/98). Directions varied in the quantity and level of detail. Conclusions: This review of UK clinical trial protocol highlights that information surrounding premature termination is lacking, with only 42% providing guidance on the care of trial participants. While this ensures regulatory compliance, it fails to consider the challenge for healthcare professionals in managing participants on-going care or the duty of care owed to participants. Further research is required to understand if additional documents are being used in practice, and if these meet the needs of healthcare professionals in supporting research participants and families during premature trial termination.
Toward a Comprehensive Model of Medical-Dental-Behavioral Integration
Authors: McNeil D.W. , Pereira D.B. , Ensz O.S. , Lukose K. , Harrell G. , Feller D.B. 
Published: November 2024

Introduction: Existing models of medical-dental integration, as well as those from behavioral health care integrated with primary medical treatment, provide a basis for a truly synthesized and expanded model incorporating medical, dental, and behavioral components. Such a comprehensive model allows for collaborative health care serving patients seamlessly without disciplinary silos, promoting optimal whole-person health. This innovative approach is consistent with recent developments in the behavioral and social oral health sciences that include an imperative for their full inclusion in dental health care, research, and education. Methods: Existing models of medical-dental integration are described, along with current models from integrated primary medical and behavioral health care. Using these existing approaches as a basis, a new multilevel model is proposed to include social and cultural determinants of health. Results: Contemporary approaches to providing health care across disciplines include referral to a geographically separate entity, co-location of services, and integrated, side-by-side care. Integration of electronic health records and interoperability are necessary (but not sufficient) factors that affect transdisciplinary health care. Effective communication among health care providers and the need for interprofessional education, comprehensive training, and ongoing cross-disciplinary consultation also are noted as crucial factors in truly collaborative care. Evidence for existing models varies greatly depending on the target population and type of services provided. Conclusions: A fully integrated, transdisciplinary model of health care is possible, theoretically and practically. Combining aspects of extant integrated models and extending them provides opportunity for a greater focus on systemic factors and more emphasis on prevention. Consistent with this new model, medical and dental home concepts can be expanded to that of a person-centered health care home that includes interprofessional practice. This transdisciplinary approach contributes to greater health equity given the multilevel approach. Multidirectional integration of diverse disciplines representing the various realms of medicine, dentistry, and behavioral health care is essential for optimal health of all. Knowledge Transfer Statement: This article can be used by clinicians, scientists, administrators, and policy makers in developing and implementing integrated systems of care that provide for patients’ medical, dental, and behavioral health needs.
Group-Based Integrative Pain Management in Primary Care: A Study Protocol for Multilevel Interventions to Address Health Disparities
Authors: Chao Maria T. , Thompson-Lastad Ariana , Swedlow Pamela , Prathikanti Sudha , Hartogensis Wendy , Wolfe-Modupe Folashade , Wennik Jesse 
Published: November 2024

Background Socioeconomically disadvantaged populations have a high prevalence of chronic pain, exacerbated by social isolation, intersectional stigma, and disparities in pain assessment and treatment. Effective interventions using a multilevel, biopsychosocial approach are needed to decrease the unequal burden of pain. Group-based integrative pain management in primary care safety net clinics is a promising model to improve pain care for racially and ethnically diverse low-income people. Objective To describe a study protocol to test the impacts of 2 group-based models – group acupuncture and integrative group medical visits – on multilevel pain-related outcomes. Methods The study uses a 2x2 factorial randomized clinical trial to test two 12 week group-based models: group acupuncture and integrative group medical visits (IGMV, with psychoeducation, mind-body approaches, and social support). English or Spanish-speaking adults with chronic pain for ≥3 months receiving care in San Francisco Department of Public Health primary care clinics are eligible for the trial. All participants will receive usual care and be randomized to group acupuncture, IGMV, both, or waitlist control. The primary outcomes are changes from baseline to 3 month follow-up in pain impact and in social support for chronic pain. Secondary outcomes include pain interference, pain intensity, depression, anxiety, quality of life, and social isolation. Data will include patient-reported outcomes, electronic health record data, and qualitative interviews, focus groups and observations to assess multilevel individual, interpersonal and organizational outcomes. Discussion Multilevel approaches are needed to advance health equity in pain management. Our study contributes to knowledge of group-based integrative pain management in primary care safety net clinics to address multilevel barriers and disparities in pain care.
Different amyloid β42 preparations induce different cell death pathways in the model of SH-SY5Y neuroblastoma cells
Authors: Özdemir Alp Yigit , Hofbauerová Kateřina , Kopecký Vladimír , Novotný Jiří , Rudajev Vladimír 
Published: November 2024

AbstractAmyloid β42 (Aβ42) plays a decisive role in the pathology of Alzheimer’s disease. The Aβ42 peptide can aggregate into various supramolecular structures, with oligomers being the most toxic form. However, different Aβ species that cause different effects have been described. Many cell death pathways can be activated in connection with Aβ action, including apoptosis, necroptosis, pyroptosis, oxidative stress, ferroptosis, alterations in mitophagy, autophagy, and endo/lysosomal functions. In this study, we used a model of differentiated SH-SY5Y cells and applied two different Aβ42 preparations for 2 and 4 days. Although we found no difference in the shape and size of Aβ species prepared by two different methods (NaOH or NH4OH for Aβ solubilization), we observed strong differences in their effects. Treatment of cells with NaOH-Aβ42 mainly resulted in damage of mitochondrial function and increased production of reactive oxygen species, whereas application of NH4OH-Aβ42 induced necroptosis and first steps of apoptosis, but also caused an increase in protective Hsp27. Moreover, the two Aβ42 preparations differed in the mechanism of interaction with the cells, with the effect of NaOH-Aβ42 being dependent on monosialotetrahexosylganglioside (GM1) content, whereas the effect of NH4OH-Aβ42 was independent of GM1. This suggests that, although both preparations were similar in size, minor differences in secondary/tertiary structure are likely to strongly influence the resulting processes. Our work reveals, at least in part, one of the possible causes of the inconsistency in the data observed in different studies on Aβ-toxicity pathways.
Graphical Abstract
Genome wide identification of BjSWEET gene family and drought response analysis of BjSWEET12 and BjSWEET17 genes in Brassica juncea
Authors: Heng Shuangping , He Jingjuan , Zhu Xinyu , Cai Jiayu , Fu Mengke , Zhang Shaoheng , Zeng Wei , Xing Feng , Mao Guangzhi 
Published: November 2024

Abstract
Background
Sugars Will Eventually be Exported Transporter (SWEET) gene family is a unique type of sugar transporter that plays a vital role in metabolic regulation, growth, development, and stress response in multiple species. This study aimed to systematically identify the SWEET gene family members and detect the regulation of gene expression and their potential roles of the SWEET gene family in Brassica juncea.

Results
A total of 66 BjSWEET (Brassica juncea Sugar Will Eventually be Exported Transporter) genes distributed across 17 chromosomes were identified. The gene structure and motifs were relatively conserved, with all members containing the MtN3/saliva domain. Phylogenetic analysis revealed that the SWEET gene family can be classified into four subfamilies (Clades I, II, III, and IV). Collinearity analysis revealed that there were 118 pairs of segment duplicates, indicating that some BjSWEET genes were obtained via segmental duplication. The promoter regions of the BjSWEET genes contained many plant hormone-related response elements, stress-related response elements, growth and development elements, and light-responsive regulatory elements. Furthermore, analysis of the expression profiles revealed that the expression levels of the BjSWEET genes differed among the eight different tissues. qRT‒PCR analysis of six selected BjSWEET genes revealed that the expression levels of BjSWEET17.2, BjSWEET17.4, BjSWEET12.2, and BjSWEET12.3 were significantly upregulated under drought treatment, suggesting that these genes may respond to drought stress in B. juncea.

Conclusion
This study systematically identified and analyzed the SWEET gene family members in B. juncea for the first time, laying the foundation for further research on the molecular mechanisms of drought resistance in B. juncea and providing theoretical guidance for the application of these genes in other species.
Fundamental care in the emergency room: insights from patients with life-threatening conditions in the emergency room
Authors: Pavedahl Veronica , Muntlin Åsa , Von Thiele Schwarz Ulrica , Summer Meranius Martina , Holmström Inger K. 
Published: November 2024

Abstract
Background
Persons who become life-threateningly ill or injured (due to for example trauma or cardiac arrest) are cared for in hospitals’ designated emergency rooms at the emergency department (ED). In these rooms, the life-threatening condition and biomedical focus may reinforce a culture that value the medical-technical care. Meeting patients fundamental care needs (integrating physical, psychosocial and relational care needs) in a person-centred way might hence be challenging in emergency rooms. Little is known about how person-centred fundamental care is experienced and valued by vulnerable and exposed patients in emergency rooms. This study aims to describe fundamental care needs experienced by patients with a life-threating condition in the emergency room.

Methods
A descriptive deductive qualitative study with individual interviews were carried out with 15 patients who had been life-threateningly ill or injured and admitted in an emergency room, in Sweden. Data collection was conducted during 2022. Transcribed interviews were analyzed with deductive content analysis, based on the Fundamentals of Care framework.

Results
Despite being life-threateningly ill or injured, patients were still able to describe their unique needs—which were not only related to biomedical care. A relationship was established between healthcare professionals and the patient in the initial stage, but not maintained during their stay at the emergency room. Patients felt their physical needs were met to a greater extent than psychosocial and relational needs, despite their prioritizing the latter. Patients preferred personalized care but described care as task oriented. The physical environment limited patients from having their fundamental care needs met, and they adopted to a “patient role” to avoid adding to staff stress. The emergency room situation evoked existential thoughts.

Conclusions
This paper provides unique insights into patients’ experiences of being cared for in an emergency room. From the patient perspective, physical care was not enough. Relationship, timely and personalized information, and existential needs were identified as essential fundamental care needs, which were not, or only partly met. The finding highlights the need to embed and prioritize fundamental care in practice also for patients who are life-threateningly ill or injured, which in turn calls for focus on organizational prerequisites to enable person-centred fundamental care.
Widespread asymmetries of amygdala nuclei predict auditory verbal hallucinations in schizophrenia
Authors: Dumitru Magda L. , Johnsen Erik , Kroken Rune A. , Løberg Else-Marie , Lilleskare Lin , Ersland Lars , Hugdahl Kenneth 
Published: November 2024

Abstract
Background
Auditory verbal hallucinations, which frequently involve negative emotions, are reliable symptoms of schizophrenia. Brain asymmetries have also been linked to the condition, but the relevance of asymmetries within the amygdala, which coordinates all emotional signals, to the content of and response to auditory verbal hallucinations has not been explored.

Methods
We evaluated the performance of two asymmetry biomarkers that were recently introduced in literature: the distance index, which captures global asymmetries, and a revised version of the laterality index, which captures left–right local asymmetries. We deployed random forest regression models over values computed with the distance index and with the laterality index over amygdala nuclei volumes (lateral, basal, accessory-basal, anterior amygdaloid area, central, medial, cortical, cortico-amygdaloid area, and paralaminar) for 71 patients and 71 age-matched controls.

Results
Both biomarkers made successful predictions for the 35 items of the revised version of the Belief About Voices Questionnaire, such that hallucination severity increased with increasing local asymmetries and with decreasing global asymmetries of the amygdala.

Conclusions
Our findings highlight a global reorganization of the amygdala, where left and right nuclei volumes differ pairwise but become proportionally more similar as hallucinations increase in severity. Identifying asymmetries in particular brain structures relevant to specific symptoms could help monitor the evolution and outcome of psychopathological conditions.
Transcriptional and post-transcriptional regulation of CARMN and its anti-tumor function in cervical cancer through autophagic flux blockade and MAPK cascade inhibition
Authors: Zhang Xing , Yan Wenjing , Jin Hua , Yu Bingjia , Zhang Hao , Ding Bo , Chen Xue , Zhang Yan , Xia Qianqian , Meng Dan , Hu Jing , Liu Haohan , Nie Yamei , Liu Fengying , Zheng Yun , Lu Yiran , Wang Juan , Du Mulong , Wang Meilin , Yu Evan Yi-Wen , Li Xiuting , Wang Shizhi 
Published: November 2024

Abstract
Background
LncRNAs play essential roles in multiple tumors. However, research on genome-wide lncRNA alterations and their functions in cervical cancer (CC) is limited. This study aims to explore key lncRNAs in CC progression and uncover the molecular mechanisms involved in the development of CC.

Methods
In this study, we analyzed 30 tissues from CC, cervical intraepithelial neoplasia (CIN), and normal (NOR) using transcriptome sequencing and weighted gene co-expression network analysis to establish gene modules related to the NOR-CIN-CC transition. Machine learning diagnostic models were employed to investigate the role of lncRNAs in this transition. Molecular biological experiments were conducted to elucidate the potential mechanisms of CARMN in CC, with a particular focus on its transcriptional and post-transcriptional regulation of abnormal expression in CC.

Results
CARMN was identified as a hub gene in two modules significantly associated with the NOR-CIN-CC transition. Analysis using ten machine learning models confirmed its critical role in this progression. The results of RNA-seq, qPCR and RNAScope performed in another cohort of 83 cervical tissues all showed that CARMN was significantly downregulated in CC. CARMN significantly enhanced the interaction between Keap1 and Nrf2, leading to increased ROS levels. The elevated ROS levels suppressed the Akt/mTOR signaling pathway, leading to autophagy arrest via autophagic flux blockade. Additionally, CARMN interacted with TFAP2α to repress MAPK13 transcription, further inhibiting the MAPK cascade. A promoter SNP (rs12517403) was found to increase CC risk (OR = 1.34, 95% CI = 1.11–1.61) and reduce CARMN expression by decreasing SP1 binding. Furthermore, the RNA binding proteins that could modulate CARMN RNA stability were also determined using RNA-pulldown assay. The results demonstrated that YBX1, a component of the coding region instability determinant (CRD)-mediated mRNA stabilization complex, promoted CARMN RNA stability. DHX9, another component of complex, acted as a scaffold to bridge YBX1 and CARMN.

Conclusions
CARMN exerts an anti-cancer effect in CC progression by inhibiting the Akt-mTOR and MAPK signaling pathways. rs12517403 and the YBX1/DHX9 complex are key mechanisms influencing its transcription and stability in CC cells. CARMN represents a promising biomarker for CC diagnosis and therapeutic target.
New chemometrics-assisted spectrophotometric methods for simultaneous determination of co-formulated drugs montelukast, rupatadine, and desloratadine in their different dosage combinations
Authors: Sharkawi Marco M. Z. , Farid Nehal F. , Hassan Moataz H. , Hassan Said A. 
Published: November 2024

AbstractTwo accurate, precise and robust multivariate chemometric methods were developed for the simultaneous determination of montelukast sodium (MON), rupatadine fumarate (RUP) and desloratadine (DES). These methods provide a cost-effective alternative to chromatographic techniques by utilizing spectrophotometry in pharmaceutical quality control. The proposed approaches, partial least squares-1 (PLS-1) and artificial neural network (ANN), were optimized using genetic algorithm (GA) to select the most influential wavelengths, enhancing model performance. A five-level, three-factor design was employed to construct a calibration set with 25 mixtures, utilizing concentration ranges of 3–19, 5–25, and 4–20 µg.mL−1 for MON, RUP, and DES, respectively. An independent validation set was employed to assess the performance of the models. GA significantly improved the PLS-1 and ANN models for RUP and DES, though minimal enhancement was observed for MON. These methods were successfully applied to the simultaneous quantification of the compounds in pharmaceutical formulations and proved useful as stability-indicating assays for RUP, given that DES is a known degradation product. The developed methods offer a valuable tool for impurity profiling and quality control in pharmaceutical analysis.
Assessing disordered eating behaviours and attitudes: Factor structure and measurement invariance of the Arabic version of the eating attitudes test (EAT-26) in Saudi Arabia
Authors: Alyami Mohsen M. , Al-Dossary Saeed A. 
Published: November 2024

Abstract
Background
The factorial structure of the Eating Attitudes Test (EAT-26) has been found to be inconsistent across studies and samples. This study aimed to resolve inconsistencies in the factorial structure of the Arabic version of the EAT-26 by identifying the best-fitting model and test its measurement invariance across sexes and BMI categories in a large non-clinical Saudi sample.

Methods
1,734 Saudi adults (Mage 26.88 and SD 9.13), predominantly female, completed an online survey. Several existing models were tested (e.g., original 26-item three-factor model, second order 26-item three-factor model, 20-item four-factor model, and 16-item four-factor model) using confirmatory factor analysis (CFA). Fit indices including the CFI, SRMR, and RMSEA were used to identify the best-fitting model for Arabic version of the EAT-26. Multi-group confirmatory factor analysis (MGCFA) was used to test measurement invariance.

Results
The original three-factor model and two other common models demonstrated poor fit (e.g., CFI = 0.727; SRMR = 0.0911; RMSEA = 0.085 [90% CI 0.082–0.087] for the original three-factor model). Instead, a 16-item, four-factor structure [(Self-Perceptions of Body Weight), (Dieting), (Awareness of Food Contents), and (Food Preoccupation)] showed acceptable fit ([CFI = 0.904; SRMR = 0.0554; RMSEA = 0.073 [90% CI 0.068- 0.077]). Internal consistency was good (α and ω = 0.88), and measurement invariance was supported across sex (male and female) and BMI categories (underweight, normal weight, overweight, and obese).

Conclusions
These findings underscore the need for culturally relevant validation of the EAT-26 among Arabic-speaking populations, as the revised factorial structure diverged from previously established models. Future research should further examine this revised 16-item, four-factor structure in clinical settings.