bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning for prediction of asthma exacerbations among asthmatic patients: a systematic review and meta-analysis
Authors: Xiong Shiqiu , Chen Wei , Jia Xinyu , Jia Yang , Liu Chuanhe
Published: July 2023

Background

Asthma exacerbations reduce the patient’s quality of life and are also responsible for significant disease burdens and economic costs. Machine learning (ML)-based prediction models have been increasingly developed to predict asthma exacerbations in recent years. This systematic review and meta-analysis aimed to identify the prediction performance of ML-based prediction models for asthma exacerbations and address the uncertainty of whether modern ML methods could become an alternative option to predict asthma exacerbations.

Methods

PubMed, Cochrane Library, EMBASE, and Web of Science were searched for studies published up to December 15, 2022. Studies that applied ML methods to develop prediction models for asthma exacerbations among asthmatic patients older than five years and were published in English were eligible. The prediction model risk of bias assessment tool (PROBAST) was utilized to estimate the risk of bias and the applicability of included studies. Stata software (version 15.0) was used for the random effects meta-analysis of performance measures. Subgroup analyses stratified by ML methods, sample size, age groups, and outcome definitions were conducted.

Results

Eleven studies, including 23 prediction models, were identified. Most of the studies were published in recent three years. Logistic regression, boosting, and random forest were the most used ML methods. The most common important predictors were systemic steroid use, short-acting beta2-agonists, emergency department visit, age, and exacerbation history. The overall pooled area under the curve of the receiver operating characteristics (AUROC) of 11 studies (23 prediction models) was 0.80 (95% CI 0.77–0.83). Subgroup analysis based on different ML models showed that boosting method achieved the best performance, with an overall pooled AUROC of 0.84 (95% CI 0.81–0.87).

Conclusion

This study identified that ML was the potential tool to achieve great performance in predicting asthma exacerbations. However, the methodology within these models was heterogeneous. Future studies should focus on improving the generalization ability and practicability, thus driving the application of these models in clinical practice.
Development of a chemically defined medium for Paenibacillus polymyxa by parallel online monitoring of the respiration activity in microtiter plates
Authors: Goldmanns Jennifer , Röhling Georg Andreas , Lipa Marie Kristine , Scholand Theresa , Deitert Alexander , May Tobias , Haas Evangeline Priya , Boy Matthias , Herold Andrea , Büchs Jochen
Published: July 2023

Background

One critical parameter in microbial cultivations is the composition of the cultivation medium. Nowadays, the application of chemically defined media increases, due to a more defined and reproducible fermentation performance than in complex media. In order, to improve cost-effectiveness of fermentation processes using chemically defined media, the media should not contain nutrients in large excess. Additionally, to obtain high product yields, the nutrient concentrations should not be limiting. Therefore, efficient medium optimization techniques are required which adapt medium compositions to the specific nutrient requirements of microorganisms.

Results

Since most Paenibacillus cultivation protocols so far described in literature are based on complex ingredients, in this study, a chemically defined medium for an industrially relevant Paenibacillus polymyxa strain was developed. A recently reported method, which combines a systematic experimental procedure in combination with online monitoring of the respiration activity, was applied and extended to identify growth limitations for Paenibacillus polymyxa. All cultivations were performed in microtiter plates. By systematically increasing the concentrations of different nutrient groups, nicotinic acid was identified as a growth-limiting component. Additionally, an insufficient buffer capacity was observed. After optimizing the growth in the chemically defined medium, the medium components were systematically reduced to contain only nutrients relevant for growth. Vitamins were reduced to nicotinic acid and biotin, and amino acids to methionine, histidine, proline, arginine, and glutamate. Nucleobases/-sides could be completely left out of the medium. Finally, the cultivation in the reduced medium was reproduced in a laboratory fermenter.

Conclusion

In this study, a reliable and time-efficient high-throughput methodology was extended to investigate limitations in chemically defined media. The interpretation of online measured respiration activities agreed well with the growth performance of samples measured in parallel via offline analyses. Furthermore, the cultivation in microtiter plates was validated in a laboratory fermenter. The results underline the benefits of online monitoring of the respiration activity already in the early stages of process development, to avoid limitations of medium components, oxygen limitation and pH inhibition during the scale-up.
The effect of low-dose aspirin on aspirin triggered lipoxin, interleukin 1 beta, and prostaglandin E2 levels in periapical fluid: a double-blind randomized clinical trial
Authors: Khoshbin Elham , Salehi Razieh , Behroozi Rooholah , Sadr Soroush , Zamani Alireza , Farhadian Maryam , Karkehabadi Hamed
Published: July 2023

Background

The role of pro-resolving mediators in inflammation is a new concern in research. The effect of low-dose aspirin on production of a special kind of these mediators named aspirin triggered lipoxin (ATL) has been studied on different tissues. This randomized clinical trial evaluated the effect of low-dose aspirin on ATL and pro-inflammatory mediators’ level in periapical fluid of necrotic teeth with large lesions.

Methods

Twenty-four patients with necrotic pulp and periapical lesion were randomly assigned to low-dose aspirin and placebo groups. In the first appointment, canals were shaped up to F3 size and #40 K-file and cleaned with 10 milliliters 2.5% sodium hypochlorite and 17% Ethylenediaminetetraacetic acid. Periapical fluid was sampled by a paper cone. The tooth was temporized without any intracanal medication. Tablets were administered for 7 days, then the teeth were re-opened and the sampling were repeated. Interleukin-1 beta (IL-1β), prostaglandin E2 (PGE2) and ATL were analyzed by enzyme-linked immunosorbent assay. Data were analyzed with paired t-test using SPSS statistical software, version 21 (α = 0.05).

Results

A significant reduction in PGE2 and IL-1β was noted in the aspirin-treated group while an increase in ATL was observed (P < 0.001). There was no significant difference in the mediator scores before and after in the placebo-treated group (P > 0.05).

Conclusion

Low-dose aspirin can influence the inflammatory process by reducing pro-inflammatory mediators such as PGE2 and IL-1β, as well as increasing the pro-resolving mediators such as ATL.

Trial registration

IRCT20191211045702N1.
GEMIN4, a potential therapeutic targets for patients with basal-like subtype breast cancer
Authors: Wu Liang , Zhang Yue , Zheng Chunlei , Zhao Fuqiang , Lin Yan
Published: July 2023

Background

Basal-like breast cancer (BLBC) takes up about 10–20% of all breast cancer(BC), what’s more, BLBC has the lowest survival rate among all BC subtypes because of lacks of efficient treatment methods. We aimed to explore the molecules that can be used as diagnostic maker for BLBC at early stage and provide optimized treatment strategies for BLBC patients in this study.

Methods

Apply weighted gene co-expression network analysis (WGCNA) to identify gene modules related to BLBC;The functional enrichment of candidate genes related to BLBC in the red module of Go data package and KEGG analysis;Overlapping cross analysis of URGs and WGCNA to identify candidate genes in each BC subtype;Divide BCBL patients into high-risk and low-risk groups, and analyze the two groups of overall survival (OS) and relapse free survival (RFS);Screening of GEMIN4 dependent cell lines; QRT PCR was used to verify the expression of GEMIN4 transfected with siRNA; CCK8 was used to determine the effect of GEMIN4 on cell viability; Positive cell count detected by BrdU staining;GO and KEGG enrichment analysis of GEMIN4.

Results

The "red module" has the highest correlation with BLBC, with 913 promising candidate genes identified from the red module;913 red module candidate genes related to BLBC participated in multiple GO terms, and KEGG enrichment analysis results mainly enriched in estrogen signaling pathways and pathways in cancer;There are 386 overlapping candidate genes among the 913 "red module" genes identified by 1893 common URG and WGCNA;In BLBC patients, 9 highly expressed genes are associated with OS. Five highly expressed genes are associated with RFS. Kaplan Meier survival analysis suggests that high GEMIN4 expression levels are associated with poor prognosis in BLBC patients;The GEMIN4 gene dependency score in HCC1143 and CAL120 cell lines is negative and low; Si-GEMIN4-1 can significantly reduce the mRNA expression of GEMIN4; Si-GEMIN4 can inhibit cell viability; Si-GEMIN4 can reduce the number of positive cells;GO enrichment analysis showed that GEMIN4 is associated with DNA metabolism processes and adenylate binding; KEGG pathway enrichment analysis shows that GEMIN4 is related to ribosome biogenesis in eukaryotes.

Conclusion

We hypothesized thatGEMIN4may be the potential target for the treatment of BLBC.
Functional polymorphism in miR-208 is associated with increased risk for ischemic stroke
Authors: Liu Chao , Luo Yan-Ping , Chen Jie , Weng Yin-Hua , Lan Yan , Liu Hong-Bo
Published: July 2023

Background

The miR-208 gene is one of the microRNAs now under active studies, and has been found to play significant roles in an array of cardiovascular diseases. Nevertheless, until now, no studies have examined the relationship between the susceptibility to ischemic stroke (IS) and genetic variations in miR-208. This study explored the association between the miR-208 polymorphisms (rs178642, rs8022522, and rs12894524) and the risk of IS.

Methods

A total of 205 cases of IS and 211 control subjects were included. The SNPscans genotyping test was employed to determine the genotypes of the three polymorphisms.

Results

Significant correlation was observed between rs8022522 polymorphism and risk of IS on the basis of analyses of genotypes, models and alleles (GA vs. GG: adjusted OR = 2.159, 95% CI: 1.052–4.430, P = 0. 036; AA vs. GG: adjusted OR = 5.154, 95% CI: 1.123–23.660, P = 0.035; dominant model: adjusted OR = 1.746, 95% CI, 1.075–2.838, P = 0.025; G vs. A: adjusted OR = 2.451, 95% CI: 1.374–4.370, P = 0.002).

Conclusions

The rs8022522 polymorphism of the miR-208 gene is significantly associated with an elevated risk of ischemic stroke in Chinese.
Generalisation of genomic findings and applications of polygenic risk scores
Authors: Corpas Manuel , Fatumo Segun
Published: July 2023

Polygenic Risk Scores (PRS) (also known as polygenic scores, genetic risk scores or polygenic indexes) capture genetic contributions of a multitude of markers that characterise complex traits. Although their likely application to precision medicine remains to be established, promising advances have included their ability to stratify high risk individuals and targeted screening interventions. Current PRS have been mostly optimised for individuals of Northern European ancestries. If PRS are to become widespread as a tool for healthcare applications, more diverse populations and greater capacity for derived interventions need to be accomplished. In this editorial we aim to attract submissions from the research community that highlight current challenges in development of PRS applications at scale. We also welcome manuscripts that delve into the ethical, social and legal implications that the implementation of PRS may generate.
Biotransformation of triterpenoid ganoderic acids from exogenous diterpene dihydrotanshinone I in the cultures of Ganoderma sessile
Authors: Wang Xinwei , Wu Haibo , Wong Ka Hong , Wang Yixuan , Chen Baixiong , Feng Kun
Published: July 2023

Background

Triterpenoids have shown a wide range of biological activities including antitumor and antiviral effects. Typically, triterpenes are synthesized through the mevalonate pathway and are extracted from natural plants and fungi. In this work, triterpenoids, ganoderic acids (GAs) were discovered to be produced via biotransformation of a diterpene, 15,16-dihydrotanshinone I (DHT) in the liquid cultured Ganoderma sessile mycelium.

Results

Firstly, the biotransformation products, two rare GAs were isolated and purified by column chromatography, and characterized using HR-ESI-MS spectrometry and NMR spectrometry. The two compounds were Lanosta-7,9(11),24-trien-15α,22,β-diacetoxy-3β-hydroxy-26-oic acid (LTHA) and Lanosta-7,9(11),24-trien-15α,22,β-diacetoxy-3β-carbonyl-26-oic acid (LTCA). Then, transcriptome and proteome technologies were employed to measure the expression of mRNA and protein, which further confirmed that triterpenoid GAs could be transformed from exogenous diterpenoid DHT. At the molecular level, we proposed a hypothesis of the mechanism by which DHT converted to GAs in G. sessile mycelium, and the possible genes involved in biotransformation were verified by RT-qPCR.

Conclusions

Two rare GAs were obtained and characterized. A biosynthetic pathway of GAs from DHT was proposed. Although the synthetic route was not confirmed, this study provided important insights into omics resources and candidate genes for studying the biotransformation of diterpenes into triterpenes.
Erdheim-Chester disease with bilateral orbital masses and multi-systemic symptoms: two case reports
Authors: Qiao JunYi , Ma Ruixin , Peng Xiaolin , He Weimin
Published: July 2023

Background

Erdheim–Chester disease (ECD) is a rare histiocytic disorder characterized by multisystem xanthogranulomatous infiltration by lipid-laden histiocytes. We report two cases of ECD involving the orbit and describe their clinicopathologic factors, treatments, and prognosis. One was a rare case of ECD complicated with primary thrombocytosis.

Case presentation

This study describes two patients with bilateral orbital ECD. Both presented with proptosis and visual loss; imaging findings showed bilateral intraorbital masses. Both had different degrees of systemic symptoms (pleural effusion, pericardial effusion, ascites, and heart failure) before the ocular symptoms and did not find the cause before ophthalmic tumor resection and pathological biopsy. The diagnosis of ECD was confirmed after pathological biopsy and detection of BRAFV600E mutation. Patient 2 also with primary thrombocytosis and had a CALR mutation as well as the BRAFV600E mutation. Both patients were recommended to receive targeted therapy. Patient 1 refused targeted therapy for financial reasons and was discharged after local radiotherapy only. The patient had no light perception in either eye and no improvement in systemic symptoms. Patient 2 began targeted treatment after diagnosis and reached the discharge criteria 2 weeks later. He is in good condition at present, but unfortunately, his eyesight has not improved because of the irreversible damage to his visual function.

Conclusion

ECD is easily misdiagnosed and missed because of its rarity and diverse clinical manifestations. Orbital involvement is common in ECD, and surgery is the most frequently employed approach. Despite the surgical resection is not curative, its significance lies in biopsy to establish diagnosis and/or surgical debulking to relieve mass effect, minimizing further impairment of visual function. Targeted therapy is the most effective treatment for patients with a positive BRAF mutation gene. Evaluation of a concomitant myeloid neoplasm is also critical before initiating targeted therapies for refractory ECD.
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

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

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

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

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

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

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

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

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

Background

In 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.

Methods

Of 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).

Results

The 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.

Conclusions

The 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

Glioblastoma (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

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.
Young videogamers and their approach to science inquiry
Authors: Avvisati Francesco , Borgonovi Francesca
Published: July 2023

Background

Written instructions seldom need to be read when playing videogames. Instead, gaming often involves early information foraging and expansive exploration behaviors. We use data from the Programme for International Student Assessment (PISA) to explore whether students who regularly play videogames (daily gamers) adopt behaviors that are typical of gaming while they complete a computer-based assessment of science and if such behaviors matter for performance in procedural science knowledge.

Methods

We use item-level data from PISA 2018 from countries that administered the optional ICT questionnaire. Using a sample item and the full set of interactive science items, we develop regression models to estimate differences between daily gamers and other students in information harvesting, time to first action, and procedural science knowledge. We report average associations across countries, country-specific estimates, as well as differences between boys and girls. We report raw differences as well as differences adjusting for background characteristics. To account for the multilevel nature of the data and for the two-stage sampling design, we use replicate weights supplied with the PISA database to estimate robust standard errors using balanced repeated replication (BRR).

Results

In 2018, 33% 15-year-olds reported playing videogames every day or almost every day. Among boys, that proportion was 49%. Daily gamers do not differ from other students in science content knowledge and in reading fluency. Nevertheless, daily gamers spend marginally less time reading instructions and display more active exploration behaviors in the assessment on items that include simulation tools.

Conclusions

Science teachers and assessment developers may find inspiration in games to develop scenarios in which students can practice effective strategies for information harvesting. The extensive exploration of a problem space in order to obtain data in support of future decisions often corresponds to a positive behaviour with multiple advantages in authentic problem situations. By contrast, fast transitions into action may, in the particular situation of an assessment, be an inadequate response. Assessment developers can ensure that instructions are carefully read and understood by test takers and teachers and can guide their students to read instructions adequately.
Olanzapine treatment effectively relieves breakthrough chemotherapy-induced nausea and vomiting: a real-world experience
Authors: Uchiike Akihiro , Kono Haruka , Miura Katsuhiro , Hayama Tatsuya , Tsutsumi Daisuke , Tsuboi Shinya , Ohtsuka Susumu , Hidaka Shinji
Published: July 2023

Background

Olanzapine treatment prevents chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC). However, its role in the secondary prevention of breakthrough CINV in real-world cancer care should be further evaluated.

Method

We conducted a retrospective study on patients receiving olanzapine to prevent breakthrough CINV refractory to standard antiemetic therapy. The major outcome was improvement in CINV, defined as any downgrade in CINV symptoms, according to the Common Terminology Criteria for Adverse Events. Comprete response was defined as no symptoms in CINV, i.e., Grade 0. These outcomes were compared in the HEC versus non-HEC groups and the standard- (5 or 10 mg/day) versus low- (2.5 mg/day) dose groups. The other outcome measurement was adverse events (AEs).

Results

We analyzed 127 patients, including 92 women, with a median age of 50 years (range: 19–89 years). Baseline CINV severity was grade 1, 2, and 3 in 18%, 69%, and 13% of the patients, respectively. After prophylaxis with olanzapine at doses of 2.5, 5, or 10 mg/day, improvement was observed in 105 (83%) patients, with a complete response in 42 patients (33%). The improvement and complete remission rates for the HEC (n = 96) and non-HEC (n = 31) groups were 86% and 71% (p = 0.048) versus 38% and 19% (p = 0.062), respectively. The rates for the standard- (n = 98) and low- (n = 29) dose groups were 86% and 82% (p = 0.568) versus 28% and 52% (p = 0.015), respectively. Thirty-four patients (27%) experienced olanzapine-related AEs, mainly somnolence (n = 28). Grade 3 or higher AEs were not observed.

Conclusion

Our study results support the clinical application of olanzapine for the secondary prevention of breakthrough CINV.
Effects of Drop Sets on Skeletal Muscle Hypertrophy: A Systematic Review and Meta-analysis
Authors: Sødal Lena Kristiansen , Kristiansen Eirik , Larsen Stian , van den Tillaar Roland
Published: July 2023

Background

One of the most popular time-efficient training methods when training for muscle hypertrophy is drop sets, which is performed by taking sets to concentric muscle failure at a given load, then making a drop by reducing the load and immediately taking the next set to concentric or voluntary muscle failure. The purpose of this systematic review and meta-analysis was to compare the effects of drop sets over traditional sets on skeletal muscle hypertrophy.

Methods

This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The SPORTDiscus and MEDLINE/PubMed databases were searched on April 9, 2022, for all studies investigating the effects of the drop set training method on muscle hypertrophy that meets the predefined inclusion criteria. Comprehensive Meta-Analysis Version 3 (Biostat Inc., Englewood Cliffs, NJ, USA) was used to run the statistical analysis. Publication bias was assessed through visual inspection of the funnel plots for asymmetry and statistically by Egger’s regression test with an alpha level of 0.10.

Results

Six studies met the predefined inclusion criteria. The number of participants in the studies was 142 (28 women and 114 men) with an age range of 19.2–27 years. The average sample size was 23.6 ± 10.9 (range 9–41). Five studies were included in the quantitative synthesis. Meta-analysis showed that both the drop set and traditional training groups increased significantly from pre- to post-test regarding muscle hypertrophy (drop set standardized mean difference: 0.555, 95% CI 0.357–0.921, p < 0.0001; traditional set standardized mean difference: 0.437, 95% CI 0.266–0.608, p < 0.0001). No significant between-group difference was found (standardized mean difference: 0.155, 95% CI − 0.199 to − 0.509, p = 0.392).

Conclusions

The results of this systematic review and meta-analysis indicate that drop sets present an efficient strategy for maximizing hypertrophy in those with limited time for training. There was no significant difference in hypertrophy measurements between the drop set and traditional training groups, but some of the drop set modalities took half to one-third of the time compared with traditional training.