bluuebunny/crossref_metadata_2025_split huggingface dataset:
INES: Interactive tool for construction and extrapolation of partitioned survival models
Authors: Gimeno-Ballester Vicente , Perez-Troncoso Daniel , Olry-Labry Antonio , Epstein David 
Published: July 2023

Abstract
Background
INES (INteractive model for Extrapolation of Survival and cost) provides an open-access tool powered by R that implements three-state partitioned survival models (PSM). This article describes the properties of the tool, and the situations where INES may or may not be suitable.

Methods
INES is designed to be used by investigators or healthcare professionals who have a good grasp of the principles of economic evaluation and understand the strengths and weaknesses of partitioned survival models, but are not sufficiently familiar with a statistical package such as Excel or R to be able to construct and test a de-novo PSM themselves.
INES is delivered to the user via a batch file. Once downloaded to the user’s hard drive, it interacts with the user via a portable version of R with web interactivity built in Shiny. INES requires absolutely no knowledge of R and the user does not need to have R or any of its dependences installed. Hence the user will deal with a standalone Shiny app. Inputs (digitalized survival curves, unit costs, posology, hazard ratios, discount rate) can be uploaded from a template spreadsheet.

Results
The INES application provides a seamlessly integrated package for estimating a set of parametric hazard functions for progression free and overall survival, selecting an appropriate function from this menu, and applying this as an input to a PSM to calculate mean costs and quality-adjusted life years. Examples are given that may serve as a tutorial.

Conclusion
INES offers a rapid, flexible, robust and transparent tool for parametric survival analysis and calculating a PSM that can be used in many different contexts.
ATP-P2X7R-mediated microglia senescence aggravates retinal ganglion cell injury in chronic ocular hypertension
Authors: Wei Miao , Zhang Guowei , Huang Zeyu , Ding Xuemeng , Sun Qing , Zhang Yujian , Zhu Rongrong , Guan Huaijin , Ji Min 
Published: July 2023

Abstract
Background
Dysfunction of microglia during aging affects normal neuronal function and results in the occurrence of neurodegenerative diseases. Retinal microglial senescence attributes to retinal ganglion cell (RGC) death in glaucoma. This study aims to examine the role of ATP-P2X7R in the mediation of microglia senescence and glaucoma progression.

Methods
Forty-eight participants were enrolled, including 24 patients with primary open-angle glaucoma (POAG) and age-related cataract (ARC) and 24 patients with ARC only. We used ARC as the inclusion criteria because of the availability of aqueous humor (AH) before phacoemulsification. AH was collected and the adenosine triphosphate (ATP) concentration was measured by ATP Assay Kit. The chronic ocular hypertension (COH) mouse model was established by microbead occlusion. Microglia were ablated by feeding PLX5622 orally. Mouse bone marrow cells (BMCs) were prepared and infused into mice through the tail vein for the restoration of microglia function. Western blotting, qPCR and ELISA were performed to analyze protein and mRNA expression in the ocular tissue, respectively. Microglial phenotype and RGC survival were assessed by immunofluorescence. The mitochondrial membrane potential was measured using a JC-1 assay kit by flow cytometry.

Results
ATP concentrations in the AH were increased in older adults and patients with POAG. The expression of P2X7R was upregulated in the retinal tissues of mice with glaucoma, and functional enrichment analysis showed that P2X7R was closely related to cell aging. Through in vivo and in vitro approaches, we showed that pathological activation of ATP-P2X7R induced accelerated microglial senescence through impairing PTEN-induced kinase 1 (PINK1)-mediated mitophagy, which led to RGC damage. Additionally, we found that replacement of senescent microglia in COH model of old mice with BMCs from young mice reversed RGC damage.

Conclusion
ATP-P2X7R induces microglia senescence by inhibiting PINK1-mediated mitophagy pathway. Specific inhibition of ATP-P2X7R may be a fundamental approach for targeted therapy of RGC injury in microglial aging-related glaucoma.
The effect of silver nanoparticles on learning and memory in rodents: "a systematic review"
Authors: Safaei Farshad , Farimaneh Javad , Rajabi Mohammad Abad Ali , Iranmanesh Ehsan , Arabpour Fatemeh , Doostishoar Farzad , Taherizadeh Zahra 
Published: July 2023

Abstract
Background
Silver nanoparticles (AgNPs) are widely used in medicine owing to their antiseptic activity and inducing cell death. Despite AgNPs' importance in nano-engineering and medical benefits, animal studies have shown silver toxicity can damage multiple organs such as the lungs, liver, kidneys, intestines, and brain. Several investigations revealed the correlation between Ag administration by different methods with impaired cognitive and behavioral abilities. Therefore, this systematic review aimed to conclude on the existing evidence of impairments in learning and memory that were changed in rodents exposed to AgNPs.

Methods
Main searches were retrieved in Google Scholar, Scopus, Web of Science, and PubMed databases from 1979 to 2022. Eligibility Criteria were applied to select and extract 15 articles among 892.

Results
Learning and memory abilities of rats and mice in screened studies were evaluated with MWM, NORT, PAL, T-maze, Y-maze, contextual fear conditioning, Radial Arm Maze and Carousel Maze test. Data have shown various sizes from 10 to 100 nm could affect the results of tests among animals exposed to AgNPs compared with control animals. However, in some treatments, results achieved from tests have not demonstrated significant differences between control and treated groups.

Conclusion
Studies have revealed that treatment with Ag-NPs of different sizes can impair learning and memory skills in rats and mice.
Study protocol: biomechanical testing, finite element analysis and prospective, randomized, clinical study of single screw cephalomedullary nailing versus integrated dual interlocking screw fixation for unstable (31A21–3) intertrochanteric fractures in patients > 70 years old
Authors: Panagopoulos Andreas , Argyropoulou Evangelia , Kokkalis Zinon T. , Parchas Nicolaos , Tserpes Konstantinos 
Published: July 2023

Abstract
Background
Hip fractures are an increasingly common consequence of falls in older people that are associated with a high risk of death and reduced function. The vast majority of intertrochanteric fractures require surgical treatment to withstand early mobilization and weight bearing, which prevents complications due to prolonged bed rest and aids in fracture healing.

Methods
This study is compromised by two parts, the experimental study and the clinical part. In the first part, a standard 130° nail will be used with the appropriate lag screw(s) and dynamic distal locking in synthetic osteoporotic femurs and the transmission of forces in the proximal femur, measured by a cortical surface-strain distribution, will be evaluated using digital image correlation. Finite element parametric models of the bone, the nails and their interface will be also developed. Finite element computations of surface strains in implanted femurs, after being validated against biomechanical testing measurements, will be used to assist the comparison of the nails by deriving important data on the developed stress and strain fields, which cannot be measured through biomechanical testing. In the other part, will set up a prospective, randomized, comparative clinical study among the Gamma3 and IT cephalomedullary nailing, in order to investigate if there are any statistical important differences in the main radiological measurements and functional status in closed unstable intertrochanteric fractures (A21-3) in patients aged over 70 years old at the 24-week follow-up evaluation using patient reported disease-specific outcomes.

Discussion
This study will be the first to compare clinical, radiological and biomechanical measurements of the two different cephalomedullary nails. Our main hypothesis is that the IT nail would provide better radiological outcome and probably better clinical results than the Gama3 nail.
Clinical trial registration International Standard Randomized Controlled Trial Number (ISRCTN): https://doi.org/10.1186/ISRCTN15588442, registered on 19/4/2022.
Exercise-induced irisin improves follicular dysfunction by inhibiting IRE1α-TXNIP/ROS-NLRP3 pathway in PCOS
Authors: Weng Yajing , Zhang Yaling , Wang Daojuan , Wang Rong , Xiang Zou , Shen Shanmei , Wang Hongwei , Wu Xiaoke , Wen Yanting , Wang Yong 
Published: July 2023

Abstract
Background
Excessive production of androgen drives oxidative stress (OS) and inflammasome activation in ovarian granulosa cells (GCs). Therefore, the induced follicular developmental disorder is the major cause of infertility in women with polycystic ovary syndrome (PCOS). Exercise-induced upregulation of irisin is capable of regulating metabolism by reducing OS and inflammation. Exercise has been shown to alleviate a range of PCOS symptoms, including maintaining a normal menstrual cycle, in several clinical trials.

Methods
Female Sprague–Dawley (SD) rats and primary ovarian cells were treated with two different androgens, dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT), to simulate a hyperandrogenic environment, followed by eight weeks of exercise training and irisin intervention. The levels of reactive oxygen species (ROS), tissue inflammation and fibrosis were examined using hematoxylin and eosin (H&E) staining, western blot, quantitative real-time PCR (qRT-PCR), dichlorofluorescein diacetate (DCF-DA) probe detection, immunofluorescence staining, immunohistochemistry, and Sirius red staining.

Results
Exercise for eight weeks improved polycystic ovarian morphology and decreased the levels of inflammation, OS, and fibrosis in PCOS rats. Hyperandrogen increased ROS production in ovarian cells by inducing endoplasmic reticulum stress (ERS) and activating the inositol-requiring enzyme 1α (IRE1α)-thioredoxin-interacting protein (TXNIP)/ROS-NOD-like receptor family pyrin domain containing 3 (NLRP3) signaling pathway, further enhancing the levels of inflammation. Irisin suppressed the expression of IRE1α and its downstream targets, thus improving the ovarian dysfunction of PCOS rats induced by hyperandrogen.

Conclusion
Exercise can alleviate various phenotypes of PCOS rats induced by DHEA, and its therapeutic effect may be mediated by secreting beneficial myokines. IRE1α may be an important target of irisin for reducing OS and inflammation, thereby improving ovarian fibrosis.
How clinicians discuss patients’ donor registrations of consent and presumed consent in donor conversations in an opt-out system: a qualitative embedded multiple-case study
Authors: van Oosterhout Sanne P. C. , van der Niet Anneke G. , Abdo W. Farid , Boenink Marianne , Cherpanath Thomas G. V. , Epker Jelle L. , Kotsopoulos Angela M. , van Mook Walther N. K. A. , Sonneveld Hans P. C. , Volbeda Meint , Olthuis Gert , van Gurp Jelle L. P. 
Published: July 2023

Abstract
Background
The Netherlands introduced an opt-out donor system in 2020. While the default in (presumed) consent cases is donation, family involvement adds a crucial layer of influence when applying this default in clinical practice. We explored how clinicians discuss patients’ donor registrations of (presumed) consent in donor conversations in the first years of the opt-out system.

Methods
A qualitative embedded multiple-case study in eight Dutch hospitals. We performed a thematic analysis based on audio recordings and direct observations of donor conversations (n = 15, 7 consent and 8 presumed consent) and interviews with the clinicians involved (n = 16).

Results
Clinicians’ personal considerations, their prior experiences with the family and contextual factors in the clinicians’ profession defined their points of departure for the conversations. Four routes to discuss patients’ donor registrations were constructed. In the Consent route (A), clinicians followed patients’ explicit donation wishes. With presumed consent, increased uncertainty in interpreting the donation wish appeared and prompted clinicians to refer to “the law” as a conversation starter and verify patients’ wishes multiple times with the family. In the Presumed consent route (B), clinicians followed the law intending to effectuate donation, which was more easily achieved when families recognised and agreed with the registration. In the Consensus route (C), clinicians provided families some participation in decision-making, while in the Family consent route (D), families were given full decisional capacity to pursue optimal grief processing.

Conclusion
Donor conversations in an opt-out system are a complex interplay between seemingly straightforward donor registrations and clinician-family interactions. When clinicians are left with concerns regarding patients’ consent or families’ coping, families are given a larger role in the decision. A strict uniform application of the opt-out system is unfeasible. We suggest incorporating the four previously described routes in clinical training, stimulating discussions across cases, and encouraging public conversations about donation.
Deacetylation of FOXP1 by HDAC7 potentiates self-renewal of mesenchymal stem cells
Authors: Ling Shifeng , Chen Tienan , Wang Shaojiao , Zhang Wei , Zhou Rujiang , Xia Xuechun , Yao Zhengju , Fan Ying , Ning Song , Liu Jiayin , Qin Lianju , Tucker Haley O. , Wang Niansong , Guo Xizhi 
Published: July 2023

Abstract
Background
Mesenchymal stem cells (MSCs) are widely used in a variety of tissue regeneration and clinical trials due to their multiple differentiation potency. However, it remains challenging to maintain their replicative capability during in vitro passaging while preventing their premature cellular senescence. Forkhead Box P1 (FOXP1), a FOX family transcription factor, has been revealed to regulate MSC cell fate commitment and self-renewal capacity in our previous study.

Methods
Mass spectra analysis was performed to identify acetylation sites in FOXP1 protein. Single and double knockout mice of FOXP1 and HDAC7 were generated and analyzed with bone marrow MSCs properties. Gene engineering in human embryonic stem cell (hESC)-derived MSCs was obtained to evaluate the impact of FOXP1 key modification on MSC self-renewal potency.

Results
FOXP1 is deacetylated and potentiated by histone deacetylase 7 (HDAC7) in MSCs. FOXP1 and HDAC7 cooperatively sustain bone marrow MSC self-renewal potency while attenuating their cellular senescence. A mutation within human FOXP1 at acetylation site (T176G) homologous to murine FOXP1 T172G profoundly augmented MSC expansion capacity during early passages.

Conclusion
These findings reveal a heretofore unanticipated mechanism by which deacetylation of FOXP1 potentiates self-renewal of MSC and protects them from cellular senescence. Acetylation of FOXP1 residue T172 as a critical modification underlying MSC proliferative capacity. We suggest that in vivo gene editing of FOXP1 may provide a novel avenue for manipulating MSC capability during large-scale expansion in clinical trials.
Menstrual blood-derived mesenchymal stromal cells: impact of preconditioning on the cargo of extracellular vesicles as potential therapeutics
Authors: de Pedro María Ángeles , López Esther , González-Nuño Francisco Manuel , Pulido María , Álvarez Verónica , Marchena Ana María , Preußer Christian , Szymański Witold , Pogge von Strandmann Elke , Graumann Johannes , Sánchez-Margallo Francisco Miguel , Casado Javier G. , Gómez-Serrano María 
Published: July 2023

Abstract
Background
Mesenchymal stromal cells (MSCs) have been shown to exert their therapeutic effects through the secretion of broad spectrum of paracrine factors, including extracellular vesicles (EVs). Accordingly, EVs are being pursued as a promising alternative to cell-based therapies. Menstrual blood-derived stromal cells (MenSCs) are a type of MSC that, due to their immunomodulatory and regenerative properties, have emerged as an innovative source. Additionally, new strategies of cell priming may potentially alter the concentration and cargo of released EVs, leading to modification of their biological properties. In this study, we aimed to characterize the EVs released by MenSCs and compare their therapeutic potential under three different preconditioning conditions (proinflammatory stimuli, physioxia, and acute hypoxia).

Methods
MenSCs were isolated from five healthy women. Following culturing to 80% confluence, MenSCs were exposed to different priming conditions: basal (21% O2), proinflammatory stimuli (IFNγ and TNFα, 21% O2), physioxia (1–2% O2), and acute hypoxia (< 1% O2) for 48–72 h. Conditioned media from MenSCs was collected after 48 h and EVs were isolated by a combination of ultra-filtration and differential centrifugation. An extensive characterization ranging from nano-flow cytometry (nFC) to quantitative high-throughput shotgun proteomics was performed. Bioinformatics analyses were used to derive hypotheses on their biological properties.

Results
No differences in the morphology, size, or number of EVs released were detected between priming conditions. The proteome analysis associated with basal MenSC-EVs prominently revealed their immunomodulatory and regenerative capabilities. Furthermore, quantitative proteomic analysis of differentially produced MenSC-EVs provided sufficient evidence for the utility of the differential preconditioning in purpose-tailoring EVs for their therapeutic application: proinflammatory priming enhanced the anti-inflammatory, regenerative and immunomodulatory capacity in the innate response of EVs, physioxia priming also improves tissue regeneration, angiogenesis and their immunomodulatory capacity targeting on the adaptive response, while acute hypoxia priming, increased hemostasis and apoptotic processes regulation in MenSC-EVs, also by stimulating immunomodulation mainly through the adaptive response.

Conclusions
Priming of MenSCs under proinflammatory and hypoxic conditions affected the cargo proteome of EVs released, resulting in different therapeutic potential, and thus warrants experimental exploration with the aim to generate better-defined MSC-derived bioproducts.
Psychometric properties of the Pride in Eating Pathology Scale in a Spanish population
Authors: Rodríguez-Testal Juan Francisco , Trinidad-Montero Juana M. , Rosales Becerra Ángela , Faija Cintia , Senín-Calderón Cristina 
Published: July 2023

AbstractBackgroundIn its relation to eating disorders, pride is one of the self-conscious emotions least analyzed, and requires valid and reliable instruments for its measurement. This study aimed to examine the factor structure and the psychometric properties of the Pride in Eating Pathology Scale (PEP-S), in the Spanish general population, as well as between-sex differences in PEP-S scores.MethodsOf the 1483 participants aged 18 to 34 (M = 21.99;SD = 3.09), 954 were women (65.2%) and the majority were university students (78.8%). Psychometric properties of the scale were tested in a cross-sectional design using cross-validation, i.e., exploratory and confirmatory factor analysis, and estimation of invariance (sex).ResultsThe four-factor structure found was similar to the original scale with invariance across sex and internal consistency (ordinal alpha .99) and stability (.85). Evidence of convergent validity and differences between sexes were found. Specifically, women scored higher on all the factors, including the healthier sense of pride.ConclusionsThe PEP-S scale is an instrument with evidence of validity and reliability in the Spanish population. Although it still has to be tested in a clinical population, it constitutes a promising instrument for the evaluation of the self-conscious emotion, pride.
Decoding key cell sub-populations and molecular alterations in glioblastoma at recurrence by single-cell analysis
Authors: Wang Xin , Sun Qian , Wang Weiwen , Liu Baohui , Gu Ying , Chen Liang 
Published: July 2023

AbstractGlioblastoma (GBM) is the most frequent malignant brain tumor, the relapse of which is unavoidable following standard treatment. However, the effective treatment for recurrent GBM is lacking, necessitating the understanding of key mechanisms driving tumor recurrence and the identification of new targets for intervention. Here, we integrated single-cell RNA-sequencing data spanning 36 patient-matched primary and recurrent GBM (pGBM and rGBM) specimens, with 6 longitudinal GBM spatial transcriptomics to explore molecular alterations at recurrence, with each cell type characterized in parallel. Genes involved in extracellular matrix (ECM) organization are preferentially enriched in rGBM cells, and MAFK is highlighted as a potential regulator. Notably, we uncover a unique subpopulation of GBM cells that is much less detected in pGBM and highly expresses ECM and mesenchyme related genes, suggesting it may contribute to the molecular transition of rGBM. Further regulatory network analysis reveals that transcription factors, such as NFATC4 and activator protein 1 members, may function as hub regulators. All non-tumor cells alter their specific sets of genes as well and certain subgroups of myeloid cells appear to be physically associated with the mesenchyme-like GBM subpopulation. Altogether, our study provides new insights into the molecular understanding of GBM relapse and candidate targets for rGBM treatment.
3D occlusal changes of upper first molars after rapid maxillary expansion on permanent versus deciduous teeth: a retrospective multicenter CBCT study
Authors: Serafin Marco , Fastuca Rosamaria , Zecca Piero Antonio , Lagravère Manuel , Caprioglio Alberto 
Published: July 2023

Abstract
Background
The purpose of this study was to compare the three-dimensional dental changes for the maxillary first molars and the overall skeletal effects achieved after expansion between the rapid maxillary expansion (RME) appliance attached to two different anchor units, the maxillary deciduous molars and the maxillary permanent first molars.

Methods
Patients were retrospectively selected according to the anchorage unit used for RME: deciduous upper second molars (RME-E group; 10 M, 10 F; mean age 8.4 ± 1.1 years) and first upper permanent molars (RME-6 group; 10 M, 10 F; mean age 12.6 ± 1.8 years). CBCT scans were obtained before treatment start (T1) and after retention and removal of the expander (T2). Images were analyzed using a new three-dimensional intra-hemi-maxillary reference system. 3D landmarks were marked to calculate all changes on maxillary first permanent molars; mesio-distal and buccal-lingual inclination and rotation, as well as intermolar and interforaminal distances were calculated. The Wilcoxon test was used to compare within-group changes, whereas the Mann–Whitney test was used to compare between-group differences, with the significance level set at 0.05.

Results
In the RME-E group, significant distorotation and lingual inclination of the first permanent molars at T2 were observed (p < 0.01); in the RME-6 group, only the buccolingual inclination of the crossbite side after RME was resulted statistically significant (p < 0.01). In both groups, intermolar and interforaminal values increased significantly (p < 0.01). Intergroup analysis showed a significantly higher distorotation and reduced buccal inclination of maxillary first permanent molars in the RME-E group after RME (p < 0.01).

Conclusions
RME is effective in treating maxillary transverse hypoplasia; RME anchored too deciduous teeth spontaneously reduces buccal inclination and increases distorotation of maxillary first permanent molars, whereas anchorage to permanent molars is associated with increased buccal inclination, albeit with little clinical significance.