bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using unfolding case studies to develop critical thinking for Graduate Entry Nursing students: an educational design research study
Authors: Macdiarmid Rachel , Merrick Eamon , Winnington Rhona 
Published: June 2024

Abstract
Background
Graduate Entry Nursing (GEN) programmes have been introduced as another entry point to nurse registration. In the development of a new GEN programme, a problem-based approach to learning was used to develop critical thinking and clinical reasoning skills of motivated and academically capable students.

Objective
To explore and evaluate the design and delivery of course material delivered to GEN students embedded in authentic learning pedagogy from the perspectives of both GEN students and academic staff using an unfolding case study approach.

Methods
An educational design research approach was used to explore the learning experiences of GEN students using an unfolding case study approach situated in experiential pedagogy and the teaching experiences of the academics who designed it. Data were collected through semi-structured interviews with students once they had finished the course and weekly reflective diary recordings by academic staff throughout implementation. Thematic analysis was used to analyse the data.

Findings
Student reflections highlighted that this cohort had insight into how they learned and were comfortable voicing their needs to academic staff. While the unfolding case studies were not liked by all participants, for some it offered a unique learning opportunity; particularly when scaffolded with podcasts, simulation labs, tutorials and clinical placements. Staff reflections primarily aligned with student experiences.

Conclusion
The gaps highlighted in the delivery of the course suggest that a blended pedagogical approach to graduate entry nurse education is required. Specifically, GEN students are aware of the learning needs and are happy to express these to academic staff, thus suggesting that engaging with a co-design curriculum approach will benefit future cohorts.
Network proximity analysis as a theoretical model for identifying potential novel therapies in primary sclerosing cholangitis
Authors: Leighton Jessica , Jones David E. J. , Dyson Jessica K. , Cordell Heather J. 
Published: June 2024

AbstractPrimary Sclerosing Cholangitis (PSC) is a progressive cholestatic liver disease with no licensed therapies. Previous Genome Wide Association Studies (GWAS) have identified genes that correlate significantly with PSC, and these were identified by systematic review. Here we use novel Network Proximity Analysis (NPA) methods to identify already licensed candidate drugs that may have an effect on the genetically coded aspects of PSC pathophysiology.Over 2000 agents were identified as significantly linked to genes implicated in PSC by this method. The most significant results include previously researched agents such as metronidazole, as well as biological agents such as basiliximab, abatacept and belatacept. This in silico analysis could potentially serve as a basis for developing novel clinical trials in this rare disease.
Adipocyte pyroptosis occurs in omental tumor microenvironment and is associated with chemoresistance of ovarian cancer
Authors: Lin Chang-Ni , Liang Yu-Ling , Tsai Hsing-Fen , Wu Pei-Ying , Huang Lan-Yin , Lin Yu-Han , Kang Chieh-Yi , Yao Chao-Ling , Shen Meng-Ru , Hsu Keng-Fu 
Published: June 2024

Abstract
Background
Ovarian carcinoma (OC) is a fatal malignancy, with most patients experiencing recurrence and resistance to chemotherapy. In contrast to hematogenous metastasizing tumors, ovarian cancer cells disseminate within the peritoneal cavity, especially the omentum. Previously, we reported omental crown-like structure (CLS) number is associated with poor prognosis of advanced-stage OC. CLS that have pathologic features of a dead or dying adipocyte was surrounded by several macrophages is well known a histologic hallmark for inflammatory adipose tissue. In this study, we attempted to clarify the interaction between metastatic ovarian cancer cells and omental CLS, and to formulate a therapeutic strategy for advanced-stage ovarian cancer.

Methods
A three-cell (including OC cells, adipocytes and macrophages) coculture model was established to mimic the omental tumor microenvironment (TME) of ovarian cancer. Caspase-1 activity, ATP and free fatty acids (FFA) levels were detected by commercial kits. An adipocyte organoid model was established to assess macrophages migration and infiltration. In vitro and in vivo experiments were performed for functional assays and therapeutic effect evaluations. Clinical OC tissue samples were collected for immunochemistry stain and statistics analysis.

Results
In three-cell coculture model, OC cells-derived IL-6 and IL-8 could induce the occurrence of pyroptosis in omental adipocytes. The pyroptotic adipocytes release ATP to increase macrophage infiltration, release FFA into TME, uptake by OC cells to increase chemoresistance. From OC tumor samples study, we demonstrated patients with high gasdermin D (GSDMD) expression in omental adipocytes is highly correlated with chemoresistance and poor outcome in advanced-stage OC. In animal model, by pyroptosis inhibitor, DSF, effectively retarded tumor growth and prolonged mice survival.

Conclusions
Omental adipocyte pyroptosis may contribute the chemoresistance in advanced stage OC. Omental adipocytes could release FFA and ATP through the GSDMD-mediate pyroptosis to induce chemoresistance and macrophages infiltration resulting the poor prognosis in advanced-stage OC. Inhibition of adipocyte pyroptosis may be a potential therapeutic modality in advanced-stage OC with omentum metastasis.
Causal association between circulating blood cell traits and pulmonary embolism: a mendelian randomization study
Authors: Jiang Chen , Lin Jianing , Xie Bin , Peng Meijuan , Dai Ziyu , Mai Suyin , Chen Qiong 
Published: June 2024

Abstract
Background
Pulmonary embolism (PE) is a life-threatening thromboembolic disease for which there is limited evidence for effective prevention and treatment. Our goal was to determine whether genetically predicted circulating blood cell traits could influence the incidence of PE.

Methods
Using single variable Mendelian randomization (SVMR) and multivariate Mendelian randomization (MVMR) analyses, we identified genetic associations between circulating blood cell counts and lymphocyte subsets and PE. GWAS blood cell characterization summary statistics were compiled from the Blood Cell Consortium. The lymphocyte subpopulation counts were extracted from summary GWAS statistics for samples from 3757 individuals that had been analyzed by flow cytometry. GWAS data related to PE were obtained from the FinnGen study.

Results
According to the SVMR and reverse MR, increased levels of circulating white blood cells (odds ratio [OR]: 0.88, 95% confidence interval [CI]: 0.81-0.95, p = 0.0079), lymphocytes (OR: 0.90, 95% CI: 0.84-0.97, p = 0.0115), and neutrophils (OR: 0.88, 95% CI: 0.81–0.96, p = 0.0108) were causally associated with PE susceptibility. MVMR analysis revealed that lower circulating lymphocyte counts (OR: 0.84, 95% CI: 0.75-0.94, p = 0.0139) were an independent predictor of PE. According to further MR results, this association may be primarily related to HLA-DR+ natural killer (NK) cells.

Conclusions
Among European populations, there is a causal association between genetically predicted low circulating lymphocyte counts, particularly low HLA-DR+ NK cells, and an increased risk of PE. This finding supports observational studies that link peripheral blood cells to PE and provides recommendations for predicting and preventing this condition.

Graphical Abstract
Targeting mTOR signaling pathways in multiple myeloma: biology and implication for therapy
Authors: Wang Yanmeng , Vandewalle Niels , De Veirman Kim , Vanderkerken Karin , Menu Eline , De Bruyne Elke 
Published: June 2024

AbstractMultiple Myeloma (MM), a cancer of terminally differentiated plasma cells, is the second most prevalent hematological malignancy and is incurable due to the inevitable development of drug resistance. Intense protein synthesis is a distinctive trait of MM cells, supporting the massive production of clonal immunoglobulins or free light chains. The mammalian target of rapamycin (mTOR) kinase is appreciated as a master regulator of vital cellular processes, including regulation of metabolism and protein synthesis, and can be found in two multiprotein complexes, mTORC1 and mTORC2. Dysregulation of these complexes is implicated in several types of cancer, including MM. Since mTOR has been shown to be aberrantly activated in a large portion of MM patients and to play a role in stimulating MM cell survival and resistance to several existing therapies, understanding the regulation and functions of the mTOR complexes is vital for the development of more effective therapeutic strategies. This review provides a general overview of the mTOR pathway, discussing key discoveries and recent insights related to the structure and regulation of mTOR complexes. Additionally, we highlight findings on the mechanisms by which mTOR is involved in protein synthesis and delve into mTOR-mediated processes occurring in MM. Finally, we summarize the progress and current challenges of drugs targeting mTOR complexes in MM.
Impact of background music listening on anxiety in cancer patients undergoing initial radiation therapy: a randomized clinical trial
Authors: Yang Huei-Fan , Chang Wen-Wei , Chou Ying-Hsiang , Huang Jing-Yang , Liao Yu-Shiun , Liao Ting-En , Tseng Hsien-Chun , Chang Shih-Tsung , Chen Hsin Lin , Ke Ya-Fang , Tsai Pei-Fang , Chan Hsiu-Man , Chang Bo-Jiun , Hwang Yi-Ting , Tsai Hsueh-Ya , Lee Yueh-Chun 
Published: June 2024

Abstract
Background
Patients undergoing radiation therapy (RT) often experience anxiety, which may jeopardize the treatment success. The efficacy of music interventions in reducing anxiety remains contentious. This randomized trial aimed to evaluate the impact of music listening on anxiety symptoms in patients undergoing initial RT.

Methods
First-time RT patients were randomly allocated to experimental and control groups. The Brief Symptom Rating Scale (BSRS-5), Distress Thermometer (DT), and Beck Anxiety Inventory (BAI-C) were administered pre- and post-RT. Changes in physiological anxiety symptoms were monitored over 10 consecutive days starting from the first day of RT. The experimental group received music during RT; the control group did not. The generalized linear mixed model was used to estimate the pre–post difference in the BSRS-5, DT, and BAI-C scores between the music intervention and control group.

Results
This study included 50 patients each in the experimental and control groups. BSRS-5 and DT scores were significantly reduced in the experimental group post-RT (p = 0.0114 and p = 0.0023, respectively). When music listening was discontinued, these scores rebounded. While the posttest BAI-C score was significantly lower in the experimental group (p < 0.0001), the pre–post difference between the two groups was not significant (p = 0.0619). On cessation of music listening, the BAI-C score also rebounded.

Conclusions
For cancer patients undergoing initial RT, music listening intervention significantly reduced anxiety symptoms measured using the BSRS-5, DT, and BAI-C scores after two weeks. Our results demonstrate the effectiveness of music listening intervention in reducing anxiety symptoms, thereby potentially improving the quality of life of cancer patients undergoing RT.
Xinbao Pill ameliorates heart failure via regulating the SGLT1/AMPK/PPARα axis to improve myocardial fatty acid energy metabolism
Authors: Pan Linjie , Xu Zhanchi , Wen Min , Li Minghui , Lyu Dongxin , Xiao Haiming , Li Zhuoming , Xiao Junhui , Cheng Yuanyuan , Huang Heqing 
Published: June 2024

Abstract
Background
Heart failure (HF) is characterized by a disorder of cardiomyocyte energy metabolism. Xinbao Pill (XBW), a traditional Chinese medicine formulation integrating “Liushen Pill” and “Shenfu Decoction,” has been approved by China Food and Drug Administration for the treatment of HF for many years. The present study reveals a novel mechanism of XBW in HF through modulation of cardiac energy metabolism.

Methods
In vivo, XBW (60, 90, 120 mg/kg/d) and fenofibrate (100 mg/kg/d) were treated for six weeks in Sprague–Dawley rats that were stimulated by isoproterenol to induce HF. Cardiac function parameters were measured by echocardiography, and cardiac pathological changes were assessed using H&E, Masson, and WGA staining. In vitro, primary cultured neonatal rat cardiomyocytes (NRCMs) were induced by isoproterenol to investigate the effects of XBW on myocardial cell damage, mitochondrial function and fatty acid energy metabolism. The involvement of the SGLT1/AMPK/PPARα signalling axis was investigated.

Results
In both in vitro and in vivo models of ISO-induced HF, XBW significantly ameliorated cardiac hypertrophy cardiac fibrosis, and improved cardiac function. Significantly, XBW improved cardiac fatty acid metabolism and mitigated mitochondrial damage. Mechanistically, XBW effectively suppressed the expression of SGLT1 protein while upregulating the phosphorylation level of AMPK, ultimately facilitating the nuclear translocation of PPARα and enhancing its transcriptional activity. Knockdown of SGLT1 further enhanced cardiac energy metabolism by XBW, while overexpression of SGLT1 reversed the cardio-protective effect of XBW, highlighting that SGLT1 is probably a critical target of XBW in the regulation of cardiac fatty acid metabolism.

Conclusions
XBW improves cardiac fatty acid energy metabolism to alleviate HF via SGLT1/AMPK/PPARα signalling axis.
Effect of essential phospholipids on hepatic steatosis in metabolic dysfunction-associated steatotic liver disease associated with type 2 diabetes mellitus and/or hyperlipidemia and/or obesity: study protocol of a randomized, double-blind, phase IV clinical trial
Authors: Stefan Norbert , Hartleb Marek , Popovic Branko , Varona Rafael 
Published: June 2024

Abstract
Background
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a predominant chronic liver condition globally and is strongly associated with obesity, diabetes mellitus, and dyslipidemia. Essential phospholipids (EPL) are recommended as supportive treatment for managing liver conditions, including MASLD or metabolic dysfunction-associated steatohepatitis, cirrhosis, and viral hepatitis. While efficacy of EPL as an adjunctive therapy in MASLD treatment has been established earlier, certain aspects of its usage such as the impact of standard-of-care parameters, effect of EPL on quality of life (QoL) and change in symptoms evaluation in patients with MASLD remain unexplored. The proposed trial aims to assess the efficacy and safety of EPL and the subsequent QoL of patients with MASLD associated with type 2 diabetes mellitus (T2DM) and/or hyperlipidemia and/or obesity.

Methods
This is a multicenter, multinational, double-blind, randomized, two-arm, placebo-controlled, parallel-group, phase IV clinical trial. The trial is being conducted in approximately 190 patients who are randomized on a 1:1 basis either to the EPL arm (Essentiale® 1800 mg/day orally + standard of care) or placebo arm (placebo + standard of care). The primary outcome is to assess the efficacy of EPL on hepatic steatosis, as measured by transient elastography, from baseline to 6 months. The secondary outcomes include change in QoL parameters, as measured by the Chronic Liver Disease Questionnaire–metabolic dysfunction-associated steatotic liver disease/ metabolic dysfunction-associated steatohepatitis and change in symptom evaluation (using the Global Overall Symptom scale) from baseline to 6 months for symptoms, including asthenia, feeling depressed, abdominal pain/discomfort, or fatigue.

Discussion
The current protocol design will allow to comprehensively explore the efficacy of EPL added to the standard of care on hepatic steatosis and QoL and its safety in patients with MASLD associated with T2DM and/or hyperlipidemia and/or obesity by assessing various outcome measures.

Trial registration
European Union Clinical Trials Register, EudraCT, 2021–006069-39. Registered on March 13, 2022.
Interannual radial growth response of Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) to severe droughts: an analysis along a gradient of soil properties and rooting characteristics
Authors: Spangenberg Göran , Zimmermann Reiner , Küppers Manfred , Schäffer Jürgen , Hein Sebastian 
Published: June 2024

Abstract
Key message
We analyzed stem growth responses of Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) to severe drought in 2003/04 and 2018. The results showed high drought tolerance in sandy, loamy, and most silty soils, with limitations on clayey soils. This study indicates the susceptibility of Douglas-firs with shallow root systems to extreme drought and the importance of deep rooting for high drought resilience.

Context
Although Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) is considered a more drought-tolerant substitute for Norway spruce (Picea abies (L.) Karst.) in Europe, there is considerable uncertainty about the drought tolerance of Douglas-fir under climate change, specifically concerning soil properties.

Aims
This study aimed to assess the influence of soil texture, plant-available water capacity, and rooting characteristics on the interannual stem growth response of Douglas-fir when exposed to severe drought.

Methods
Along a soil texture gradient from sand to clay, we selected seven closely spaced sites at elevations of approximately 500 m a.s.l. in southern Germany. Mixed-effects models were used to analyze the effects of soil physical and rooting characteristics on growth response indices (resistance, recovery, resilience) related to the severe to extreme droughts in 2003/04 and 2018.

Results
Douglas-fir showed high drought tolerance in sandy, loamy, and most silty soils. However, the results suggest a higher drought stress risk on clayey soils, as well as at specific silty sites with shallow root systems. A higher effective rooting depth increased the resilience of Douglas-fir during the extreme drought in 2018.

Conclusion
Douglas-fir demonstrated its drought tolerance in most soil textures. In addition, this study supports the need for combined above- and below-ground investigations on factors influencing drought tolerance and the importance of rooting for drought resilience.
Subjective performance evaluation of bitrate allocation strategies for MPEG and JPEG Pleno point cloud compression
Authors: Lazzarotto Davi , Testolina Michela , Ebrahimi Touradj 
Published: June 2024

AbstractThe recent rise in interest in point clouds as an imaging modality has motivated standardization groups such as JPEG and MPEG to launch activities aiming at developing compression standards for point clouds. Lossy compression usually introduces visual artifacts that negatively impact the perceived quality of media, which can only be reliably measured through subjective visual quality assessment experiments. While MPEG standards have been subjectively evaluated in previous studies on multiple occasions, no work has yet assessed the performance of the recent JPEG Pleno standard in comparison to them. In this study, a comprehensive performance evaluation of JPEG and MPEG standards for point cloud compression is conducted. The impact of different configuration parameters on the performance of the codecs is first analyzed with the help of objective quality metrics. The results from this analysis are used to define three rate allocation strategies for each codec, which are employed to compress a set of point clouds at four target rates. The set of distorted point clouds is then subjectively evaluated following two subjective quality assessment protocols. Finally, the obtained results are used to compare the performance of these compression standards and draw insights about best coding practices.
Whole-tumoral metabolic heterogeneity in 18F-FDG PET/CT is a novel prognostic marker for neuroblastoma
Authors: Liu Jun , Ren Qinghua , Xiao Haonan , Li Siqi , Zheng Lingling , Yang Xu , Feng Lijuan , Zhou Ziang , Wang Huanmin , Yang Jigang , Wang Wei 
Published: June 2024

Abstract
Background
Neuroblastoma (NB) is a highly heterogeneous tumor, and more than half of newly diagnosed NB are associated with extensive metastases. Accurately characterizing the heterogeneity of whole-body tumor lesions remains clinical challenge. This study aims to quantify whole-tumoral metabolic heterogeneity (WMH) derived from whole-body tumor lesions, and investigate the prognostic value of WMH in NB.

Methods
We retrospectively enrolled 95 newly diagnosed pediatric NB patients in our department. Traditional semi-quantitative PET/CT parameters including the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean), the peak standardized uptake value (SUVpeak), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured. These PET/CT parameters were expressed as PSUVmax, PSUVmean, PSUVpeak, PMTV, PTLG for primary tumor, WSUVmax, WSUVmean, WSUVpeak, WMTV, WTLG for whole-body tumor lesions. The metabolic heterogeneity was quantified using the areas under the curve of the cumulative SUV-volume histogram index (AUC-CSH index). Intra-tumoral metabolic heterogeneity (IMH) and WMH were extracted from primary tumor and whole-body tumor lesions, respectively. The outcome endpoints were overall survival (OS) and progression-free survival (PFS). Survival analysis was performed utilizing the univariate and multivariate Cox proportional hazards regression. The optimal cut-off values for metabolic parameters were obtained by receiver operating characteristic curve (ROC).

Results
During follow up, 27 (28.4%) patients died, 21 (22.1%) patients relapsed and 47 (49.5%) patients remained progression-free survival, with a median follow-up of 35.0 months. In survival analysis, WMTV and WTLG were independent indicators of PFS, and WMH was an independent risk factor of PFS and OS. However, IMH only showed association with PFS and OS. In addition to metabolic parameters, the International Neuroblastoma Staging System (INSS) was identified as an independent risk factor for PFS, and neuron-specific enolase (NSE) served as an independent predictor of OS.

Conclusion
WMH was an independent risk factor for PFS and OS, suggesting its potential as a novel prognostic marker for newly diagnosed NB patients.