bluuebunny/crossref_metadata_2025_split huggingface dataset:
Empowered patients and informal care-givers as partners?—a survey study of healthcare professionals’ perceptions
Authors: Scott Duncan Therese , Riggare Sara , Bylund Ami , Hägglund Maria , Stenfors Terese , Sharp Lena , Koch Sabine 
Published: April 2023

Abstract
Background
More knowledge is needed regarding the perceptions of healthcare professionals when encountering empowered patients and informal caregivers in clinical settings. This study aimed to investigate healthcare professionals’ attitudes towards and experiences of working with empowered patients and informal caregivers, and perception of workplace support in these situations.

Methods
A multi-centre web survey was conducted using a non-probability sampling of both primary and specialized healthcare professionals across Sweden. A total of 279 healthcare professionals completed the survey. Data was analysed using descriptive statistics and Thematic analysis.

Results
Most respondents perceived empowered patients and informal caregivers as positive and had to some extent experience of learning new knowledge and skills from them. However, few respondents stated that these experiences were regularly followed-up at their workplace. Potentially negative consequences such as increased inequality and additional workload were, however, mentioned. Patients’ engagement in the development of clinical workplaces was seen as positive by the respondents, but few had own experience of such engagement and considered it difficult to be achieved .

Conclusion
Overall positive attitudes of healthcare professionals are a fundamental prerequisite to the transition of the healthcare system recognizing empowered patients and informal caregivers as partners.
Sperm-borne microRNA-34c regulates maternal mRNA degradation and preimplantation embryonic development in mice
Authors: Cui Long , Fang Li , Zhuang Lili , Shi Biwei , Lin Chao-Po , Ye Yinghui 
Published: April 2023

Abstract
Background
Studies have shown that sperm-borne microRNAs (miRNAs) are involved in mammalian preimplantation embryonic development. In humans, spermatozoan miR-34c levels are correlated with in vitro fertilization outcomes, such as embryo quality and the clinical pregnancy and live birth rates. In rabbits and cows, miR-34c improves the developmental competence of embryos generated by somatic cell nuclear transfer. However, the mechanisms underlying the regulation of embryonic development by miR-34c remain unknown.

Methods
Female C57BL/6 mice (6–8 weeks old) were superovulated, and pronucleated zygotes were collected and microinjected with an miR-34c inhibitor or a negative-control RNA. The embryonic development of the microinjected zygotes was evaluated, and the messenger RNA (mRNA) expression profiles of the embryos at the two-cell, four-cell and blastocyst stages (five embryos per group) were determined by RNA sequencing analysis. Gene expression levels were verified by reverse transcription–quantitative polymerase chain reaction. Cluster analysis and heat map visualization were performed to detect differentially expressed mRNAs. Pathway and process enrichment analyses were performed using ontology resources. Differentially expressed mRNAs were systematically analyzed using the Search Tool for the Retrieval of Interacting Genes/Proteins database to determine their biological functions.

Results
Embryonic developmental potential was significantly reduced in zygotes microinjected with the miR-34c inhibitor compared with those microinjected with a negative-control RNA. Two-cell stage embryos microinjected with an miR-34c inhibitor presented altered transcriptomic profiles, with upregulated expression of maternal miR-34c target mRNAs and classical maternal mRNAs. Differentially expressed transcripts were mainly of genes associated with lipid metabolism and cellular membrane function at the two-cell stage, with cell-cycle phase transition and energy metabolism at the four-cell stage; and with vesicle organization, lipid biosynthetic process and endomembrane system organization at the blastocyst stage. We also showed that genes related to preimplantation embryonic development, including Alkbh4, Sp1, Mapk14, Sin3a, Sdc1 and Laptm4b, were significantly downregulated after microinjection of an miR-34c inhibitor.

Conclusions
Sperm-borne miR-34c may regulate preimplantation embryonic development by affecting multiple biological processes, such as maternal mRNA degradation, cellular metabolism, cell proliferation and blastocyst implantation. Our data demonstrate the importance of sperm-derived miRNAs in the development of preimplantation embryos.
A qualitative longitudinal study of motivation in the REtirement in ACTion (REACT) physical activity intervention for older adults with mobility limitations
Authors: Cross Rosina , Greaves Colin , Withall Janet , Kritz Marlene , Stathi Afroditi 
Published: April 2023

Abstract
Background
Physical activity (PA) is beneficial for older adults’ health, however they remain the least active age group in the UK. This qualitative longitudinal study aims to understand motivations in older adults receiving the REACT physical activity intervention, through the lens of self-determination theory.

Methods
Participants were older adults randomised to the intervention arm of the Retirement in ACTion (REACT) Study, a group-based physical activity and behaviour maintenance intervention to prevent decline of physical functioning in older adults (≥ 65 years). Stratified purposive sampling by physical functioning (Short Physical Performance Battery scores) and 3-month attendance was employed. Fifty-one semi-structured interviews were conducted at 6, 12 and 24-months with twenty-nine older adults (Mean age (baseline) = 77.9 years, SD 6.86, 69% female) and at 24-months with twelve session leaders and two service managers. Interviews were audio recorded, transcribed verbatim and analysed using Framework Analysis.

Results
Perceptions of autonomy, competence and relatedness were associated with adherence to the REACT programme and maintenance of an active lifestyle. Motivational processes and participants’ support needs, changed during the 12-month REACT intervention and across the 12-months post-intervention. Group interactions were an important source of motivation during the first six months but increased competence and mobility drove motivation at the later stages (12 months) and post-intervention (24 months).

Conclusions
Motivational support needs vary in different stages of a 12-month group-based programme (adoption and adherence) and post-intervention (long-term maintenance). Strategies to accommodate those needs include, (a) making exercise social and enjoyable, (b) understanding participants’ capabilities and tailoring the programme accordingly, (c) capitalising on group support to motivate participants to try other activities and prepare sustainable active living plans.

Trial registration
The REACT study was a pragmatic multi-centre, two-arm, single-blind, parallel-group, RCT (ISRCTN registration number 45627165).
Extending inherited metabolic disorder diagnostics with biomarker interaction visualizations
Authors: Slenter Denise N. , Hemel Irene M. G. M. , Evelo Chris T. , Bierau Jörgen , Willighagen Egon L. , Steinbusch Laura K. M. 
Published: April 2023

Abstract
Background
Inherited Metabolic Disorders (IMDs) are rare diseases where one impaired protein leads to a cascade of changes in the adjacent chemical conversions. IMDs often present with non-specific symptoms, a lack of a clear genotype–phenotype correlation, and de novo mutations, complicating diagnosis. Furthermore, products of one metabolic conversion can be the substrate of another pathway obscuring biomarker identification and causing overlapping biomarkers for different disorders. Visualization of the connections between metabolic biomarkers and the enzymes involved might aid in the diagnostic process. The goal of this study was to provide a proof-of-concept framework for integrating knowledge of metabolic interactions with real-life patient data before scaling up this approach. This framework was tested on two groups of well-studied and related metabolic pathways (the urea cycle and pyrimidine de-novo synthesis). The lessons learned from our approach will help to scale up the framework and support the diagnosis of other less-understood IMDs.

Methods
Our framework integrates literature and expert knowledge into machine-readable pathway models, including relevant urine biomarkers and their interactions. The clinical data of 16 previously diagnosed patients with various pyrimidine and urea cycle disorders were visualized on the top 3 relevant pathways. Two expert laboratory scientists evaluated the resulting visualizations to derive a diagnosis.

Results
The proof-of-concept platform resulted in varying numbers of relevant biomarkers (five to 48), pathways, and pathway interactions for each patient. The two experts reached the same conclusions for all samples with our proposed framework as with the current metabolic diagnostic pipeline. For nine patient samples, the diagnosis was made without knowledge about clinical symptoms or sex. For the remaining seven cases, four interpretations pointed in the direction of a subset of disorders, while three cases were found to be undiagnosable with the available data. Diagnosing these patients would require additional testing besides biochemical analysis.

Conclusion
The presented framework shows how metabolic interaction knowledge can be integrated with clinical data in one visualization, which can be relevant for future analysis of difficult patient cases and untargeted metabolomics data. Several challenges were identified during the development of this framework, which should be resolved before this approach can be scaled up and implemented to support the diagnosis of other (less understood) IMDs. The framework could be extended with other OMICS data (e.g. genomics, transcriptomics), and phenotypic data, as well as linked to other knowledge captured as Linked Open Data.
The spectrum of imaging manifestations of Gorham–Stout disease: a novel dynamic contrast-enhanced MR lymphangiography
Authors: Lee Yuna , Lee Seunghyun , Hur Saebeom , Jeong Yun Soo , Suh Dong In , Moon Jangsup , Kim Man Jin , Choi Young Hun , Cheon Jung-Eun 
Published: April 2023

Abstract
Background
To describe the radiological features of Gorham–Stout disease (GSD) as evaluated using plain radiography and dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL) imaging techniques.

Methods
Clinical and conventional imaging data were retrospectively reviewed for 15 patients with GSD between January 2001 and December 2020. After December 2018, DCMRL examinations were performed for lymphatic vessel evaluation in patients with GSD and reviewed in four patients.

Results
The median age at diagnosis was 9 years (range: 2 months–53 years). The clinical manifestations were dyspnea in seven patients (46.7%), sepsis in 12 (80.0%), orthopedic problems in seven (46.7%), and bloody chylothorax in seven (46.7%). The common sites of osseous involvement were the spine (73.3%) and pelvic bone (60.0%). Among the non-osseous involvements, peri-osseous infiltrative soft-tissue abnormalities adjacent to the area of bone involvement were the most common (86.7%), followed by splenic cysts (26.7%) and interstitial thickening (26.7%). DCMRL demonstrated weak central conducting lymphatic flow in two patients with abnormal giant tortuous thoracic ducts and no flow in one patient. All patients who underwent DCMRL in this study presented with altered anatomical lymphatics and functional flow with collateralization.

Conclusion
DCMRL imaging and plain radiography are very useful for determining the extent of GSD. DCMRL is a novel imaging tool for the visualization of abnormal lymphatics in patients with GSD, which helps in further treatment. Therefore, in patients with GSD, it might be necessary to obtain not only plain radiographs but also MR and DCMRL images.
Microendoscopy in vivo for the pathological diagnosis of cervical precancerous lesions and early cervical cancer
Authors: Liu Min , Lu Jianqiao , Zhi Yong , Ruan Yetian , Cao Guangxu , Xu Xinxin , An Xin , Gao Jinli , Li Fang 
Published: April 2023

Abstract
Background
Cervical cancer is an important public health problem. Conventional colposcopy is inefficient in the diagnosis of cervical lesions and massive biopsies result in trauma. There is an urgent need for a new clinical strategy to triage women with abnormal cervical screening results immediately and effectively. In this study, the high-resolution microendoscopy combined with methylene blue cell staining technology was used to perform real-time in vivo imaging of the cervix for the first time.

Methods
A total of 41 patients were enrolled in the study. All patients underwent routine colposcopy and cervical biopsy, and high-resolution images of methylene blue-stained cervical lesions were obtained in vivo using microendoscopy. The cell morphological features of benign and neoplastic cervical lesions stained with methylene blue under microendoscopy were analyzed and summarized. The microendoscopy and histopathology findings of the high-grade squamous intraepithelial lesion (HSIL) and more severe lesions were compared.

Results
The overall consistency of microendoscopy diagnosis with pathological diagnosis was 95.12% (39/41). Diagnostic cell morphological features of cervicitis, low-grade squamous intraepithelial lesion (LSIL), HSIL, adenocarcinoma in situ, and invasive cancer were clearly demonstrated in methylene blue stained microendoscopic images. In HSIL and more severe lesions, microendoscopic methylene blue cell staining technology can show the microscopic diagnostic features consistent with histopathology.

Conclusions
This study was an initial exercise in the application of the microendoscopy imaging system combined with methylene blue cell staining technology to cervical precancerous lesions and cervical cancer screening. The results provided the basis for a novel clinical strategy for triage of women with abnormal cervical screening results using in vivo non-invasive optical diagnosis technology.
MYC drives platinum resistant SCLC that is overcome by the dual PI3K-HDAC inhibitor fimepinostat
Authors: Chen Jasmine , Guanizo Aleks C. , Jakasekara W. Samantha N. , Inampudi Chaitanya , Luong Quinton , Garama Daniel J. , Alamgeer Muhammad , Thakur Nishant , DeVeer Michael , Ganju Vinod , Watkins D. Neil , Cain Jason E. , Gough Daniel J. 
Published: April 2023

Abstract
Background
Small cell lung cancer (SCLC) is an aggressive neuroendocrine cancer with an appalling overall survival of less than 5% (Zimmerman et al. J Thor Oncol 14:768-83, 2019). Patients typically respond to front line platinum-based doublet chemotherapy, but almost universally relapse with drug resistant disease. Elevated MYC expression is common in SCLC and has been associated with platinum resistance. This study evaluates the capacity of MYC to drive platinum resistance and through screening identifies a drug capable of reducing MYC expression and overcoming resistance.

Methods
Elevated MYC expression following the acquisition of platinum resistance in vitro and in vivo was assessed. Moreover, the capacity of enforced MYC expression to drive platinum resistance was defined in SCLC cell lines and in a genetically engineered mouse model that expresses MYC specifically in lung tumors. High throughput drug screening was used to identify drugs able to kill MYC-expressing, platinum resistant cell lines. The capacity of this drug to treat SCLC was defined in vivo in both transplant models using cell lines and patient derived xenografts and in combination with platinum and etoposide chemotherapy in an autochthonous mouse model of platinum resistant SCLC.

Results
MYC expression is elevated following the acquisition of platinum resistance and constitutively high MYC expression drives platinum resistance in vitro and in vivo. We show that fimepinostat decreases MYC expression and that it is an effective single agent treatment for SCLC in vitro and in vivo. Indeed, fimepinostat is as effective as platinum-etoposide treatment in vivo. Importantly, when combined with platinum and etoposide, fimepinostat achieves a significant increase in survival.

Conclusions
MYC is a potent driver of platinum resistance in SCLC that is effectively treated with fimepinostat.
A comprehensive map of human glucokinase variant activity
Authors: Gersing Sarah , Cagiada Matteo , Gebbia Marinella , Gjesing Anette P. , Coté Atina G. , Seesankar Gireesh , Li Roujia , Tabet Daniel , Weile Jochen , Stein Amelie , Gloyn Anna L. , Hansen Torben , Roth Frederick P. , Lindorff-Larsen Kresten , Hartmann-Petersen Rasmus 
Published: April 2023

Abstract
Background
Glucokinase (GCK) regulates insulin secretion to maintain appropriate blood glucose levels. Sequence variants can alter GCK activity to cause hyperinsulinemic hypoglycemia or hyperglycemia associated with GCK-maturity-onset diabetes of the young (GCK-MODY), collectively affecting up to 10 million people worldwide. Patients with GCK-MODY are frequently misdiagnosed and treated unnecessarily. Genetic testing can prevent this but is hampered by the challenge of interpreting novel missense variants.

Result
Here, we exploit a multiplexed yeast complementation assay to measure both hyper- and hypoactive GCK variation, capturing 97% of all possible missense and nonsense variants. Activity scores correlate with in vitro catalytic efficiency, fasting glucose levels in carriers of GCK variants and with evolutionary conservation. Hypoactive variants are concentrated at buried positions, near the active site, and at a region of known importance for GCK conformational dynamics. Some hyperactive variants shift the conformational equilibrium towards the active state through a relative destabilization of the inactive conformation.

Conclusion
Our comprehensive assessment of GCK variant activity promises to facilitate variant interpretation and diagnosis, expand our mechanistic understanding of hyperactive variants, and inform development of therapeutics targeting GCK.
A metabolic perspective of selection for fruit quality related to apple domestication and improvement
Authors: Lin Qiong , Chen Jing , Liu Xuan , Wang Bin , Zhao Yaoyao , Liao Liao , Allan Andrew C. , Sun Chongde , Duan Yuquan , Li Xuan , Grierson Donald , Verdonk Julian C. , Chen Kunsong , Han Yuepeng , Bi Jinfeng 
Published: April 2023

AbstractBackgroundApple is an economically important fruit crop. Changes in metabolism accompanying human-guided evolution can be revealed using a multiomics approach. We perform genome-wide metabolic analysis of apple fruits collected from 292 wild and cultivated accessions representing various consumption types.ResultsWe find decreased amounts of certain metabolites, including tannins, organic acids, phenolic acids, and flavonoids as the wild accessions transition to cultivated apples, while lysolipids increase in the “Golden Delicious” to “Ralls Janet” pedigree, suggesting better storage. We identify a total of 222,877 significant single-nucleotide polymorphisms that are associated with 2205 apple metabolites. Investigation of a region from 2.84 to 5.01 Mb on chromosome 16 containing co-mapping regions for tannins, organic acids, phenolic acids, and flavonoids indicates the importance of these metabolites for fruit quality and nutrition during breeding. The tannin and acidity-related genesMyb9-likeandPH4are mapped closely to fruit weight locusfw1from 3.41 to 3.76 Mb on chromosome 15, a region under selection during domestication. Lysophosphatidylethanolamine (LPE) 18:1, which is suppressed byfatty acid desaturase-2(FAD2), is positively correlated to fruit firmness. We find the fruit weight is negatively correlated with salicylic acid and abscisic acid levels. Further functional assays demonstrate regulation of these hormone levels byNAC-like activated by Apetala3/Pistillata(NAP) andATP binding cassette G25(ABCG25), respectively.ConclusionsThis study provides a metabolic perspective for selection on fruit quality during domestication and improvement, which is a valuable resource for investigating mechanisms controlling apple metabolite content and quality.
Immunomodulatory effects of modified Liu-Wei-Di-Huang-Wan Traditional Chinese medicine on allergic asthmatic mice
Authors: Tsai Jaw-Ji , Yen Chung-Yang , Hsu Chun-Hsien , Yu Sheng-Jie , Chen Chao-Hsien , Liao En-Chih 
Published: April 2023

Abstract
Background
Allergic asthma occurs worldwide and is particularly prevalent in westernized countries characterized by chronic airway inflammation resulting in airway hyperresponsiveness. The house dust mites (HDM) including Dermatophagoides pteronyssinus are major sources of sensitization and triggering allergic symptoms in asthmatic patients. The Der p 2 is a major allergen and the predominant source of causative respiratory disorders which induce airway inflammation and bronchial constriction in mite-allergic patients. Few studies evaluate the ameliorating effects of modified Liu-Wei-Di-Huang-Wan (modified LWDHW) on allergic asthma.

Methods
This study aimed to investigate the immunological mechanisms of modified LWDHW on the reductions of airway inflammation, signal transduction, inflammatory cytokine production, Th2 cell proliferation, and bronchial obstruction in Der p 2-induced asthmatic mice.

Results
At least ten active ingredients were contained in the formula of modified LWDHW- 1217A and 1217B. Results showed that the immunoglobulin generations (Der p 2 specific- IgE and IgG1), inflammatory cytokine productions (IL-5 and IL-13) in the Sera and BALF could be down-regulated, and the Th1-cytokine productions (IL-12 and IFN-γ) be increased after immunotherapy with modified LWDHW of 1217A or 1217B. The inflammatory cell infiltrations (macrophages, eosinophils, and neutrophils) in the airway and the expressions of TH2-related genes (IL-4, IL-5, and IL-13), TH2-related transcription factor (GATA-3), and neutrophil chemotactic chemokine (IL-8) in the lung tissue of asthmatic mice were significantly decreased after the immunotherapy. The Th1/Th2 polarization had been identified that the IL-4+/CD4+ T cells were downregulated and IFN-γ+/CD4+ T cells were increased. The airway hyperresponsiveness to methacholine inhalation of Penh values was significantly decreased in the treated groups. There were significant improvements in the bronchus histopathology after immunotherapy with 1217A or 1217B which were evaluated by tracheal thickness, inflammatory cell count, and tracheal rupture of mouse lung.

Conclusion
It revealed that 1217A or 1217B could regulate the immune responses and improve pulmonary function. Data suggests that modified LWDHW of 1217A or 1217B have the potential for use as a therapeutic intervention for the treatment of mite allergen Der p 2-induced allergic asthma.