bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protease secretions by the invading blastocyst induce calcium oscillations in endometrial epithelial cells via the protease-activated receptor 2
Authors: Hennes Aurélie , Devroe Johanna , De Clercq Katrien , Ciprietti Martina , Held Katharina , Luyten Katrien , Van Ranst Nele , Maenhoudt Nina , Peeraer Karen , Vankelecom Hugo , Voets Thomas , Vriens Joris 
Published: April 2023

AbstractBackgroundEarly embryo implantation is a complex phenomenon characterized by the presence of an implantation-competent blastocyst and a receptive endometrium. Embryo development and endometrial receptivity must be synchronized and an adequate two-way dialogue between them is necessary for maternal recognition and implantation. Proteases have been described as blastocyst-secreted proteins involved in the hatching process and early implantation events. These enzymes stimulate intracellular calcium signaling pathways in endometrial epithelial cells (EEC). However, the exact molecular players underlying protease-induced calcium signaling, the subsequent downstream signaling pathways and the biological impact of its activation remain elusive.MethodsTo identify gene expression of the receptors and ion channels of interest in human and mouse endometrial epithelial cells, RNA sequencing, RT-qPCR and in situ hybridization experiments were conducted. Calcium microfluorimetric experiments were performed to study their functional expression.ResultsWe showed that trypsin evoked intracellular calcium oscillations in EEC of mouse and human, and identified the protease-activated receptor 2 (PAR2) as the molecular entity initiating protease-induced calcium responses in EEC. In addition, this study unraveled the molecular players involved in the downstream signaling of PAR2 by showing that depletion and re-filling of intracellular calcium stores occurs via PLC, IP3R and the STIM1/Orai1 complex. Finally, in vitro experiments in the presence of a specific PAR2 agonist evoked an upregulation of the ‘Window of implantation’ markers in human endometrial epithelial cells.ConclusionsThese findings provide new insights into the blastocyst-derived protease signaling and allocate a key role for PAR2 as maternal sensor for signals released by the developing blastocyst.Graphical Abstract
Transesophageal echocardiography-guided percutaneous patent ductus arteriosus closure without fluoroscopy
Authors: Wang Gang , Wu Yuhao , Pan Zhengxia , Wu Chun , Li Yonggang , Li Hongbo , Wang Quan , Liu Bo , Dai Jiangtao 
Published: April 2023

Abstract
Objectives
A retrospective study was performed to summarize the experience of transcatheter closure of patent ductus arteriosus (PDA) through the right femoral vein under the guidance of transesophageal echocardiography (TEE).

Methods
From January 2019 to September 2021, 75 children who underwent PDA closure through the right femoral vein under the guidance of TEE were included. The guide wire and delivery sheath were inserted through the ductus arteriosus into the descending aorta via the right femoral vein, and the occluder was subsequently deployed. After discharge, all patients were required for outpatient follow-ups at 1, 3, 6 and 12 months.

Results
In this group, patients were older than 10 months of age and body weight greater than 8 kg. Among 75 cases with PDA, 63 were tubular type and 12 were conical type. The mean operative time was 40.2 ± 7.3 min. The size of PDA occluder ranged from 4–6 to 12–14 mm. The mean hospital stay was 5.5 ± 0.5 days. One month after discharge, there were 4 cases with a mild residual shunt. Eventually, the residual shunt was not observed during 3, 6, and 12 months of follow-up.

Conclusions
PDA closure under the guidance of TEE can be performed through the right femoral vein successfully and effectively. This procedure has no contrast agent usage, radiation exposure, or open incisions.
Localisation of digital health tools used by displaced populations in low and middle-income settings: a scoping review and critical analysis of the Participation Revolution
Authors: Benson Jennifer , Brand Tilman , Christianson Lara , Lakeberg Meret 
Published: April 2023

AbstractBackgroundForced displacement is a crucial determinant of poor health. With 31 people displaced every minute worldwide, this is an important global issue. Addressing this, the Participation Revolution workstream from the World Humanitarian Summit’s Localisation commitments has gained traction in attempting to improve the effectiveness of humanitarian aid. Simultaneously, digital health initiatives have become increasingly ubiquitous tools in crises to deliver humanitarian assistance and address health burdens.ObjectiveThis scoping review explores how the localisation agenda’s commitment to participation has been adopted within digital health interventions used by displaced people in low-and-middle-income countries.MethodsThis review adopted the Arksey and O’Malley approach and searched five academic databases and three online literature repositories with aPopulation,ConceptandContextinclusion criteria. Data were synthesised and analysed through a critical power lens from the perspective of displaced people in low-and-middle-income-countries.Results27 papers demonstrated that a heterogeneous group of health issues were addressed through various digital health initiatives, principally through the use of mobile phones. The focus of the literature lay largely within technical connectivity and feasibility assessments, leaving a gap in understanding potential health implications. The varied conceptualisation of the localisation phenomenon has implications for the future of participatory humanitarian action: Authorship of reviewed literature primarily descended from high-income countries exposing global power dynamics leading the narrative. However, power was not a central theme in the literature: Whilst authors acknowledged the benefit of local involvement, participatory activities were largely limited to informing content adaptations and functional modifications within pre-determined projects and objectives.ConclusionWith over 100 million people displaced globally, effective initiatives that meaningfully address health needs without perpetuating harmful inequalities are an essential contribution to the humanitarian arena. The gap in health outcomes evidence, the limited constructions of health, and the varying and nuanced digital divide factors are all indicators of unequal power in the digital health sphere. More needs to be done to address these gaps meaningfully, and more meaningful participation could be a crucial undertaking to achieve this.Registration The study protocol was registered before the study (10.17605/OSF.IO/9D25R) athttps://osf.io/9d25r.
Understanding the roles and regulation patterns of circRNA on its host gene in tumorigenesis and tumor progression
Authors: Wei Jianxia , Li Mengna , Xue Changning , Chen Shipeng , Zheng Lemei , Deng Hongyu , Tang Faqing , Li Guiyuan , Xiong Wei , Zeng Zhaoyang , Zhou Ming 
Published: April 2023

AbstractCircular RNAs (circRNAs) are a novel type of endogenous non-coding RNAs, which are covalently closed loop structures formed by precursor mRNAs (pre-mRNAs) through back-splicing. CircRNAs are abnormally expressed in many tumors, and play critical roles in a variety of tumors as oncogenes or tumor suppressor genes by sponging miRNAs, regulating alternative splicing and transcription, cis-regulating host genes, interacting with RNA binding proteins (RBPs) or encoding polypeptides. Among them, the regulation of circRNAs on their corresponding host genes is a critical way for circRNAs to exit their functions. Accumulating evidence suggests that circRNAs are able to regulate the expression of host genes at the transcriptional level, post-transcriptional level, translational level, post-translational level, or by encoding polypeptides. Therefore, this paper mainly summarized the roles and association of circRNAs and their corresponding host genes in tumorigenesis and tumor progression, generalized the circRNAs that function synergistically or antagonistically with their host genes, and elaborated the mechanisms of mutual regulation between circRNAs and their host genes. More importantly, this review provides specific references for revealing the potential application of circRNAs combined with their host genes in tumor diagnosis, treatment and prognosis.
How to measure children's feet: 3D foot scanning compared with established 2D manual or digital methods
Authors: Mueller Juliane , Richter Monika , Schaefer Kathrin , Ganz Jonathan , Lohscheller Jörg , Mueller Steffen 
Published: April 2023

AbstractBackgroundIn infants and young children, a wide heterogeneity of foot shape is typical. Therefore, children, who are additionally influenced by rapid growth and maturation, are a very special cohort for foot measurements and the footwear industry. The importance of foot measurements for footwear fit, design, as well as clinical applications has been sufficiently described. New measurement techniques (3D foot scanning) allow the assessment of the individual foot shape. However, the validity in comparison to conventional methods remains unclear. Therefore, the purpose of this study was to compare 3D foot scanning with two established measurement methods (2D digital scanning/manual foot measurements).MethodsTwo hundred seventy seven children (125 m / 152 f; mean ± SD: 8.0 ± 1.5yrs; 130.2 ± 10.7cm; 28.0 ± 7.3kg) were included into the study. After collection of basic data (sex, age (yrs), body height (cm), body weight (kg)) geometry of the right foot was measured in static condition (stance) with three different measurement systems (fixed order): manual foot measurement, 2D foot scanning (2D desk scanner) and 3D foot scanning (hand‐held 3D scanner). Main outcomes were foot length, foot width (projected; anatomical; instep), heel width and anatomical foot ball breadth. Analysis of variances for dependent samples was applied to test for differences between foot measurement methods (Post‐hoc analysis: Tukey‐Kramer‐Test; α=0.05).ResultsSignificant differences were found for all outcome measures comparing the three methods (p<0.0001). The span of foot length differences ranged from 3 to 6mm with 2D scans showing the smallest and 3D scans the largest deviations. Foot width measurements in comparison of 3D and 2D scans showed consistently higher values for 3D measurements with the differences ranging from 1mm to 3mm.ConclusionsThe findings suggests that when comparing foot data, it is important to consider the differences caused by new measurement methods. Differences of about 0.6cm are relevant when measuring foot length, as this is the difference of a complete shoe size (Parisian point). Hence, correction factors may be required to compare the results of different measurements appropriately. The presented results may have relevance in the field of ergonomics (shoe industry) as well as clinical practice.
The struggle to stay physically active—A qualitative study exploring experiences of individuals with persistent plantar fasciopathy
Authors: Mørk Marianne , Soberg Helene Lundgaard , Hoksrud Aasne Fenne , Heide Marte , Groven Karen Synne 
Published: April 2023

AbstractBackgroundPlantar fasciopathy is the most common cause of heel pain, and is associated with decreased physical activity level and quality of life. There has been limited research on the experiences of patients with plantar fasciopathy. This study seeks to gain more in‐depth understanding and knowledge by exploring the lived experiences of people with persistent plantar fasciopathy.MethodsWe included 15 participants with longstanding plantar fasciopathy. Face‐to‐face, semi‐structured interviews were audio recorded, transcribed verbatim and analysed using Braun and Clark's reflexive thematic analysis. We used an inductive approach led by a phenomenological theoretical framework.ResultsWe identified three core themes and ten sub‐themes. The first theme was ‘Struggling to stay active’ with sub‐themes ‘Struggling with pain and how to adjust it’, ‘ Finding alternative activities' and ‘Longing for the experience of walking’. The second main theme was ‘Emotional challenges' with the sub‐themes ‘Feelings of frustration and self‐blame’ and ‘Worries of weight gain and related consequences'. The third main theme was ‘Relations to others' with the sub‐themes ‘Participation in family and social life’, ‘ Visible in new ways', ‘ Striving to avoid sick leave’ and ‘Bothering others'.ConclusionsParticipants revealed how their heel pain led to inactivity and emotional and social challenges. Pain when walking and fear of aggravating it dominated the participants' lives. They emphasised the importance of finding alternative ways to stay active and avoiding sick leave. Treatment should focus on holistic and individually tailored approaches.
De novo truncating variants of TRIM8 and atypical neuro-renal syndrome: a case report and literature review
Authors: Li Wei , Guo Hui 
Published: April 2023

Abstract
Background
The TRIM8 gene encodes a protein that participates in various biological processes. TRIM8 variants can lead to early termination of protein translation, which can cause a rare disease called neuro-renal syndrome. This syndrome is characterized by epilepsy, psychomotor retardation, and focal segmental glomerulosclerosis. However, we found that some patients may not present the above typical triad, and the reason may be related to their variant sites.

Case presentation
We report a case of a 6-year-old boy with nephrotic-range proteinuria as the first prominent manifestation of TRIM8 variant. He had stage 3 chronic kidney disease at the time of presentation, specific facial features, and a neurogenic bladder. He had not experienced seizures previously. There were no apparent abnormalities in his growth, intelligence, or motor development. The results of whole exome sequencing showed a TRIM8 variant. Renal biopsy revealed focal segmental glomerulosclerosis and renal tubular cystic dilatation. He did not respond to hormone and angiotensin-converting enzyme inhibitor treatment; however, the symptoms of neurogenic bladder were relieved after treatment with Solifenacin.

Conclusion
In this case, renal disease was the prominent manifestation; the patient had no other obvious neurological symptoms except a neurogenic bladder. Notably, the variant site is the closest to the C-terminal to date. Based on the analysis of previously reported cases, we found that as the TRIM8 variant became closer to the C-terminal, the renal lesions became more prominent, and there were fewer neurologic lesions. Our findings provide a new understanding of neuro-renal syndrome caused by TRIM8 variant. Patients may only have kidney disease as a prominent manifestation. At the same time, we found that we should also pay attention to the eye lesions of these patients. Therefore, gene analysis is helpful in identifying the etiology and guiding the prognosis of patients with hormone-resistant proteinuria. We suggest that TRIM8 should be included in gene panels designed for the genetic evaluation of hormone-resistant proteinuria.
Activated CD90/Thy-1 fibroblasts co-express the Δ133p53β isoform and are associated with highly inflamed rheumatoid arthritis
Authors: Wiles Anna K. , Mehta Sunali , Millier Melanie , Woolley Adele G. , Li Kunyu , Parker Kim , Kazantseva Marina , Wilson Michelle , Young Katie , Bowie Sarah , Ray Sankalita , Slatter Tania L. , Stamp Lisa K. , Hessian Paul A. , Braithwaite Antony W. 
Published: April 2023

Abstract
Background
The p53 isoform Δ133p53β is known to be associated with cancers driven by inflammation. Many of the features associated with the development of inflammation in rheumatoid arthritis (RA) parallel those evident in cancer progression. However, the role of this isoform in RA has not yet been explored. The aim of this study was to determine whether Δ133p53β is driving aggressive disease in RA.

Methods
Using RA patient synovia, we carried out RT-qPCR and RNAScope-ISH to determine both protein and mRNA levels of Δ133p53 and p53. We also used IHC to determine the location and type of cells with elevated levels of Δ133p53β. Plasma cytokines were also measured using a BioPlex cytokine panel and data analysed by the Milliplex Analyst software.

Results
Elevated levels of pro-inflammatory plasma cytokines were associated with synovia from RA patients displaying extensive tissue inflammation, increased immune cell infiltration and the highest levels of Δ133TP53 and TP53β mRNA. Located in perivascular regions of synovial sub-lining and surrounding ectopic lymphoid structures (ELS) were a subset of cells with high levels of CD90, a marker of ‘activated fibroblasts’ together with elevated levels of Δ133p53β.

Conclusions
Induction of Δ133p53β in CD90+ synovial fibroblasts leads to an increase in cytokine and chemokine expression and the recruitment of proinflammatory cells into the synovial joint, creating a persistently inflamed environment. Our results show that dysregulated expression of Δ133p53β could represent one of the early triggers in the immunopathogenesis of RA and actively perpetuates chronic synovial inflammation. Therefore, Δ133p53β could be used as a biomarker to identify RA patients more likely to develop aggressive disease who might benefit from targeted therapy to cytokines such as IL-6.
A deep learning model using chest X-ray for identifying TB and NTM-LD patients: a cross-sectional study
Authors: Liu Chia-Jung , Tsai Cheng Che , Kuo Lu-Cheng , Kuo Po-Chih , Lee Meng-Rui , Wang Jann-Yuan , Ko Jen-Chung , Shih Jin-Yuan , Wang Hao-Chien , Yu Chong-Jen 
Published: April 2023

Abstract
Background
Timely differentiating between pulmonary tuberculosis (TB) and nontuberculous mycobacterial lung disease (NTM-LD), which are radiographically similar, is important because infectiousness and treatment differ. This study aimed to evaluate whether artificial intelligence could distinguish between TB or NTM-LD patients by chest X-rays (CXRs) from suspects of mycobacterial lung disease.

Methods
A total of 1500 CXRs, including 500 each from patients with pulmonary TB, NTM-LD, and patients with clinical suspicion but negative mycobacterial culture (Imitator) from two hospitals, were retrospectively collected and evaluated in this study. We developed a deep neural network (DNN) and evaluated model performance using the area under the receiver operating characteristic curves (AUC) in both internal and external test sets. Furthermore, we conducted a reader study and tested our model under three scenarios of different mycobacteria prevalence.

Results
Among the internal and external test sets, the AUCs of our DNN model were 0.83 ± 0.005 and 0.76 ± 0.006 for pulmonary TB, 0.86 ± 0.006 and 0.64 ± 0.017 for NTM-LD, and 0.77 ± 0.007 and 0.74 ± 0.005 for Imitator. The DNN model showed higher performance on the internal test set in classification accuracy (66.5 ± 2.5%) than senior (50.8 ± 3.0%, p < 0.001) and junior pulmonologists (47.5 ± 2.8%, p < 0.001). Among different prevalence scenarios, the DNN model has stable performance in terms of AUC to detect TB and mycobacterial lung disease.

Conclusion
DNN model had satisfactory performance and a higher accuracy than pulmonologists on classifying patients with presumptive mycobacterial lung diseases. DNN model could be a complementary first-line screening tool.
Intra- and peri-tumoral MRI radiomics features for preoperative lymph node metastasis prediction in early-stage cervical cancer
Authors: Zhang Zhenhua , Wan Xiaojie , Lei Xiyao , Wu Yibo , Zhang Ji , Ai Yao , Yu Bing , Liu Xinmiao , Jin Juebin , Xie Congying , Jin Xiance 
Published: April 2023

Abstract
Background
Noninvasive and accurate prediction of lymph node metastasis (LNM) is very important for patients with early-stage cervical cancer (ECC). Our study aimed to investigate the accuracy and sensitivity of radiomics models with features extracted from both intra- and peritumoral regions in magnetic resonance imaging (MRI) with T2 weighted imaging (T2WI) and diffusion weighted imaging (DWI) for predicting LNM.

Methods
A total of 247 ECC patients with confirmed lymph node status were enrolled retrospectively and randomly divided into training (n = 172) and testing sets (n = 75). Radiomics features were extracted from both intra- and peritumoral regions with different expansion dimensions (3, 5, and 7 mm) in T2WI and DWI. Radiomics signature and combined radiomics models were constructed with selected features. A nomogram was also constructed by combining radiomics model with clinical factors for predicting LNM.

Results
The area under curves (AUCs) of radiomics signature with features from tumors in T2WI and DWI were 0.841 vs. 0.791 and 0.820 vs. 0.771 in the training and testing sets, respectively. Combining radiomics features from tumors in the T2WI, DWI and peritumoral 3 mm expansion in T2WI achieved the best performance with an AUC of 0.868 and 0.846 in the training and testing sets, respectively. A nomogram combining age and maximum tumor diameter (MTD) with radiomics signature achieved a C-index of 0.884 in the prediction of LNM for ECC.

Conclusions
Radiomics features extracted from both intra- and peritumoral regions in T2WI and DWI are feasible and promising for the preoperative prediction of LNM for patients with ECC.
Expansion and characterization of human limbus-derived stromal/mesenchymal stem cells in xeno-free medium for therapeutic applications
Authors: Sahoo Abhishek , Damala Mukesh , Jaffet Jilu , Prasad Deeksha , Basu Sayan , Singh Vivek 
Published: April 2023

Abstract
Background
Mesenchymal stem cells (MSCs) have been proven to prevent and clear corneal scarring and limbal stem cell deficiency. However, using animal-derived serum in a culture medium raises the ethical and regulatory bar. This study aims to expand and characterize human limbus-derived stromal/mesenchymal stem cells (hLMSCs) for the first time in vitro in the xeno-free medium.

Methods
Limbal tissue was obtained from therapeutic grade corneoscleral rims and subjected to explant culture till tertiary passage in media with and without serum (STEM MACS XF; SM), to obtain pure hLMSCs. Population doubling time, cell proliferation, expression of phenotypic markers, tri-lineage differentiation, colony-forming potential and gene expression analysis were carried out to assess the retention of phenotypic and genotypic characteristics of hLMSCs.

Results
The serum-free medium supported the growth of hLMSCs, retaining similar morphology but a significantly lower doubling time of 23 h (*p < 0.01) compared to the control medium. FACS analysis demonstrated ≥ 90% hLMSCs were positive for CD90+, CD73+, CD105+, and ≤ 6% were positive for CD45−, CD34−andHLA-DR−. Immunofluorescence analysis confirmed similar expression of Pax6+, COLIV+, ABCG2+, ABCB5+, VIM+, CD90+, CD105+, CD73+, HLA-DR−andCD45−, αSMA− in both the media. Tri-lineage differentiation potential and gene expression of hLMSCs were retained similarly to that of the control medium.

Conclusion
The findings of this study demonstrate successful isolation, characterization and culture optimization of hLMSCs for the first time in vitro in a serum-free environment. This will help in the future pre-clinical and clinical applications of MSCs in translational research.