bluuebunny/crossref_metadata_2025_split huggingface dataset:
The long-term effect of elexacaftor/tezacaftor/ivacaftor on cardiorespiratory fitness in adolescent patients with cystic fibrosis: a pilot observational study
Authors: Stastna Nela , Hrabovska Lenka , Homolka Pavel , Homola Lukas , Svoboda Michal , Brat Kristian , Fila Libor 
Published: May 2024

Abstract
Background
Physical activity is a crucial demand on cystic fibrosis treatment management. The highest value of oxygen uptake (VO2peak) is an appropriate tool to evaluate the physical activity in these patients. However, there are several other valuable CPET parameters describing exercise tolerance (Wpeak, VO2VT1, VO2VT2, VO2/HRpeak, etc.), and helping to better understand the effect of specific treatment (VE, VT, VD/VT etc.). Limited data showed ambiguous results of this improvement after CFTR modulator treatment. Elexacaftor/tezacaftor/ivacaftor medication improves pulmonary function and quality of life, whereas its effect on CPET has yet to be sufficiently demonstrated.

Methods
We performed a single group prospective observational study of 10 adolescent patients with cystic fibrosis who completed two CPET measurements between January 2019 and February 2023. During this period, elexacaftor/tezacaftor/ivacaftor treatment was initiated in all of them. The first CPET at the baseline was followed by controlled CPET at least one year after medication commencement. We focused on interpreting the data on their influence by the novel therapy. We hypothesized improvements in cardiorespiratory fitness following treatment. We applied the Wilcoxon signed-rank test. The data were adjusted for age at the time of CPET to eliminate bias of aging in adolescent patients.

Results
We observed significant improvement in peak workload, VO2 peak, VO2VT1, VO2VT2, VE/VCO2 slope, VE, VT, RQ, VO2/HR peak and RR peak. The mean change in VO2 peak was 5.7 mL/kg/min, or 15.9% of the reference value (SD ± 16.6; p= 0.014). VO2VT1 improved by 15% of the reference value (SD ± 0.1; p= 0.014), VO2VT2 improved by 0.5 (SD ± 0.4; p= 0.01). There were no differences in other parameters.

Conclusion
Exercise tolerance improved after elexacaftor/tezacaftor/ivacaftor treatment initiation. We suggest that the CFTR modulator alone is not enough for recovering physical decondition, but should be supplemented with physical activity and respiratory physiotherapy. Further studies are needed to examine the effect of CFTR modulators and physical therapy on cardiopulmonary exercise tolerance.
Preoperative and follow-up variations of psoas major muscle are related to S1 screw loosening in patients with degenerative lumbar spinal stenosis
Authors: Zhou Siyu , Xu Fei , Sun Zhuoran , Jiang Shuai , Li Zhuofu , Han Gengyu , Li Weishi 
Published: May 2024

Abstract
Background
It was reported the paraspinal muscle played an important role in spinal stability. The preoperative paraspinal muscle was related to S1 screw loosening. But the relationship between preoperative and postoperative change of psoas major muscle (PS) and S1 pedicle screw loosening in degenerative lumbar spinal stenosis (DLSS) patients has not been reported. This study investigated the effects of preoperative and follow-up variations in the psoas major muscle (PS) on the first sacral vertebra (S1) screw loosening in patients with DLSS.

Methods
212 patients with DLSS who underwent lumbar surgery were included. The patients were divided into the S1 screw loosening group and the S1 screw non-loosening group. Muscle parameters were measured preoperatively and at last follow-up magnetic resonance imaging. A logistic regression analysis was performed to investigate the risk factors for S1 screw loosening.

Results
The S1 screw loosening rate was 36.32% (77/212). The relative total cross-sectional areas and relative functional cross-sectional areas (rfCSAs) of the PS at L2–S1 were significantly higher after surgery. The increased rfCSA values of the PS at L3–S1 in the S1 screw non-loosening group were significantly higher than those in the S1 screw loosening group. The regression analysis showed male, lower CT value of L1 and longer segment fusion were independent risk factors for S1 screw loosening, and postoperative hypertrophy of the PS was a protective factor for S1 screw loosening.

Conclusions
Compared to the preoperative muscle, the PS size increased and fatty infiltration decreased after surgery from L2–3 to L5–S1 in patients with DLSS after short-segment lumbar fusion surgery. Postoperative hypertrophy of the PS might be considered as a protective factor for S1 screw loosening. MRI morphometric parameters and postoperative selected exercise of PS for DLSS patients after posterior lumbar fusion surgery might contribute to improvement of surgical outcome.
Regulatory and evolutionary impact of DNA methylation in two songbird species and their naturally occurring F1 hybrids
Authors: Boman Jesper , Qvarnström Anna , Mugal Carina F. 
Published: May 2024

Abstract
Background
Regulation of transcription by DNA methylation in 5’-CpG-3’ context is a widespread mechanism allowing differential expression of genetically identical cells to persist throughout development. Consequently, differences in DNA methylation can reinforce variation in gene expression among cells, tissues, populations, and species. Despite a surge in studies on DNA methylation, we know little about the importance of DNA methylation in population differentiation and speciation. Here we investigate the regulatory and evolutionary impact of DNA methylation in five tissues of two Ficedula flycatcher species and their naturally occurring F1 hybrids.

Results
We show that the density of CpG in the promoters of genes determines the strength of the association between DNA methylation and gene expression. The impact of DNA methylation on gene expression varies among tissues with the brain showing unique patterns. Differentially expressed genes between parental species are predicted by genetic and methylation differentiation in CpG-rich promoters. However, both these factors fail to predict hybrid misexpression suggesting that promoter mismethylation is not a main determinant of hybrid misexpression in Ficedula flycatchers. Using allele-specific methylation estimates in hybrids, we also determine the genome-wide contribution of cis- and trans effects in DNA methylation differentiation. These distinct mechanisms are roughly balanced in all tissues except the brain, where trans differences predominate.

Conclusions
Overall, this study provides insight on the regulatory and evolutionary impact of DNA methylation in songbirds.
Information technology-supported integrated health service for older adults in long-term care settings
Authors: Choi Jung-Yeon , Kim Hongsoo , Chun Seungyeon , Jung Young-il , Yoo Sooyoung , Oh In-Hwan , Kim Gi-Soo , Ko Jin Young , Lim Jae-Young , Lee Minho , Lee Jongseon , Kim Kwang-il 
Published: May 2024

Abstract
Background
To examine the effectiveness and safety of a data sharing and comprehensive management platform for institutionalized older patients.

Methods
We applied information technology-supported integrated health service platform to patients who live at long-term care hospitals (LTCHs) and nursing homes (NHs) with cluster randomized controlled study. We enrolled 555 patients aged 65 or older (461 from 7 LTCHs, 94 from 5 NHs). For the intervention group, a tablet-based platform comprising comprehensive geriatric assessment, disease management, potentially inappropriate medication (PIM) management, rehabilitation program, and screening for adverse events and warning alarms were provided for physicians or nurses. The control group was managed with usual care. Co-primary outcomes were (1) control rate of hypertension and diabetes, (2) medication adjustment (PIM prescription rate, proportion of polypharmacy), and (3) combination of potential quality-of-care problems (composite quality indicator) from the interRAI assessment system which assessed after 3-month of intervention.

Results
We screened 1119 patients and included 555 patients (control; 289, intervention; 266) for analysis. Patients allocated to the intervention group had better cognitive function and took less medications and PIMs at baseline. The diabetes control rate (OR = 2.61, 95% CI 1.37–4.99, p = 0.0035), discontinuation of PIM (OR = 4.65, 95% CI 2.41–8.97, p < 0.0001), reduction of medication in patients with polypharmacy (OR = 1.98, 95% CI 1.24–3.16, p = 0.0042), and number of PIMs use (ꞵ =  − 0.27, p < 0.0001) improved significantly in the intervention group. There was no significant difference in hypertension control rate (OR = 0.54, 95% CI 0.20–1.43, p = 0.2129), proportion of polypharmacy (OR = 1.40, 95% CI 0.75–2.60, p = 0.2863), and improvement of composite quality indicators (ꞵ = 0.03, p = 0.2094). For secondary outcomes, cognitive and motor function, quality of life, and unplanned hospitalization were not different significantly between groups.

Conclusions
The information technology-supported integrated health service effectively reduced PIM use and controlled diabetes among older patients in LTCH or NH without functional decline or increase of healthcare utilization.

Trial registration
Clinical Research Information Service, KCT0004360. Registered on 21 October 2019.
CircPIAS1 promotes hepatocellular carcinoma progression by inhibiting ferroptosis via the miR-455-3p/NUPR1/FTH1 axis
Authors: Zhang Xiao-Yu , Li Shan-Shan , Gu Yu-Rong , Xiao Le-Xin , Ma Xin-Yi , Chen Xin-Ru , Wang Jia-Liang , Liao Chun-Hong , Lin Bing-Liang , Huang Yue-Hua , Lian Yi-Fan 
Published: May 2024

Abstract
Background
The role of circRNAs in hepatocellular carcinoma (HCC) progression remains unclear. CircPIAS1 (circBase ID: hsa_circ_0007088) was identified as overexpressed in HCC cases through bioinformatics analysis. This study aimed to investigate the oncogenic properties and mechanisms of circPIAS1 in HCC development.

Methods
Functional analyses were conducted to assess circPIAS1’s impact on HCC cell proliferation, migration, and ferroptosis. Xenograft mouse models were employed to evaluate circPIAS1’s effects on tumor growth and pulmonary metastasis in vivo. Bioinformatics analysis, RNA immunoprecipitation, and luciferase reporter assays were utilized to elucidate the molecular pathways influenced by circPIAS1. Additional techniques, including RNA pulldown, fluorescence in situ hybridization (FISH), chromatin immunoprecipitation (ChIP), qPCR, and western blotting, were used to further explore the underlying mechanisms.

Results
CircPIAS1 expression was elevated in HCC tissues and cells. Silencing circPIAS1 suppressed HCC cell proliferation and migration both in vitro and in vivo. Mechanically, circPIAS1 overexpression inhibited ferroptosis by competitively binding to miR-455-3p, leading to upregulation of Nuclear Protein 1 (NUPR1). Furthermore, NUPR1 promoted FTH1 transcription, enhancing iron storage in HCC cells and conferring resistance to ferroptosis. Treatment with ZZW-115, an NUPR1 inhibitor, reversed the tumor-promoting effects of circPIAS1 and sensitized HCC cells to lenvatinib.

Conclusion
This study highlights the critical role of circPIAS1 in HCC progression through modulation of ferroptosis. Targeting the circPIAS1/miR-455-3p/NUPR1/FTH1 regulatory axis may represent a promising therapeutic strategy for HCC.
miR-92b-3p protects retinal tissues against DNA damage and apoptosis by targeting BTG2 in experimental myopia
Authors: Liu Jinpeng , Bao Bo , Li Tuling , Yang Zhaohui , Du Yongle , Zhang Ruixue , Xin Jizhao , Hao Jiawen , Wang Guimin , Bi Hongsheng , Guo Dadong 
Published: May 2024

Abstract
Background
Myopia is one of the eye diseases that can damage the vision of young people. This study aimed to explore the protective role of miR-92b-3p against DNA damage and apoptosis in retinal tissues of negative lens-induced myopic (LIM) guinea pigs by targeting BTG2.

Methods
Biometric measurements of ocular parameters, flash electroretinogram (FERG), and retinal thickness (RT) were performed after miR-92b-3p intravitreal injection in LIM guinea pigs. The apoptotic rate was detected by Annexin V-FITC/PI double staining, and the change in mitochondrial membrane potential was measured by JC-1 staining. Retinal apoptosis and expression of p53, BTG2, and CDK2 were explored by TdT-mediated dUTP-biotin nick labeling (TUNEL) and immunofluorescence staining assays, respectively. BTG2 and its upstream and downstream molecules at gene and protein levels in retinal tissues were measured by real-time quantitative PCR (qPCR) and Western blotting.

Results
Compared with normal controls (NC), the ocular axial length of LIM guinea pig significantly increased, whereas refraction decreased. Meanwhile, dMax-a and -b wave amplitudes of ERG declined, retinal thickness was decreased, the number of apoptotic cells and apoptotic rate in LIM eyes was exaggerated, and the mitochondrial membrane potential significantly decreased. In addition, results of qPCR and Western blot assays showed that the expression levels of p53, BTG2, CDK2, and BAX in LIM guinea pigs were higher than the levels of the NC group, whereas the BCL-2 expression level was decreased. By contrast, the miR-92b-3p intravitreal injection in LIM guinea pigs could significantly inhibit axial elongation, alleviate DNA damage and apoptosis, and thus protect guinea pigs against myopia.

Conclusion
In conclusion, p53 and BTG2 were activated in the retinal tissue of myopic guinea pigs, and the activated BTG2 could elevate the expression of CDK2 and BAX, and attenuate the expression of BCL-2, which in turn promote apoptosis and eventually lead to retinal thinning and impaired visual function in myopic guinea pigs. The miR-92b-3p intravitreal injection can attenuate the elongation of ocular length and retinal thickness, and inhibit the CDK2, BAX, and p53 expression by targeting BTG2, thereby ameliorating DNA damage and apoptosis in LIM guinea pigs and protecting ocular tissues.

Graphical Abstract
Intrauterine inflammation and postnatal intravenous dopamine alter the neurovascular unit in preterm newborn lambs
Authors: Tran Nhi T. , Hale Nadia , Maung Anawar Aung Win , Wiersma Manon , Walker David W. , Polglase Graeme , Castillo-Melendez Margie , Wong Flora Y. 
Published: May 2024

Abstract
Background
Intrauterine inflammation is considered a major cause of brain injury in preterm infants, leading to long-term neurodevelopmental deficits. A potential contributor to this brain injury is dysregulation of neurovascular coupling. We have shown that intrauterine inflammation induced by intra-amniotic lipopolysaccharide (LPS) in preterm lambs, and postnatal dopamine administration, disrupts neurovascular coupling and the functional cerebral haemodynamic responses, potentially leading to impaired brain development. In this study, we aimed to characterise the structural changes of the neurovascular unit following intrauterine LPS exposure and postnatal dopamine administration in the brain of preterm lambs using cellular and molecular analyses.

Methods
At 119–120 days of gestation (term = 147 days), LPS was administered into the amniotic sac in pregnant ewes. At 126-7 days of gestation, the LPS-exposed lambs were delivered, ventilated and given either a continuous intravenous infusion of dopamine at 10 µg/kg/min or isovolumetric vehicle solution for 90 min (LPS, n = 6; LPSDA, n = 6). Control preterm lambs not exposed to LPS were also administered vehicle or dopamine (CTL, n = 9; CTLDA, n = 7). Post-mortem brain tissue was collected 3–4 h after birth for immunohistochemistry and RT-qPCR analysis of components of the neurovascular unit.

Results
LPS exposure increased vascular leakage in the presence of increased vascular density and remodelling with increased astrocyte “end feet” vessel coverage, together with downregulated mRNA levels of the tight junction proteins Claudin-1 and Occludin. Dopamine administration decreased vessel density and size, decreased endothelial glucose transporter, reduced neuronal dendritic coverage, increased cell proliferation within vessel walls, and increased pericyte vascular coverage particularly within the cortical and deep grey matter. Dopamine also downregulated VEGFA and Occludin tight junction mRNA, and upregulated dopamine receptor DRD1 and oxidative protein (NOX1, SOD3) mRNA levels. Dopamine administration following LPS exposure did not exacerbate any effects induced by LPS.

Conclusion
LPS exposure and dopamine administration independently alters the neurovascular unit in the preterm brain. Alterations to the neurovascular unit may predispose the developing brain to further injury.
Maternal employment characteristics as a structural social determinant of breastfeeding after return to work in the European Region: a scoping review
Authors: Brugaillères Pauline , Deguen Séverine , Lioret Sandrine , Haidar Sahar , Delamaire Corinne , Counil Emilie , Vandentorren Stéphanie 
Published: May 2024

Abstract
Background
The European Region has the lowest rate of exclusive breastfeeding at 6 months worldwide. Improving work-related breastfeeding issues is important given that women may have difficulties combining work and breastfeeding, especially those in precarious working situations, which adds to their adversity. This scoping review overviews research on the maternal employment characteristics that support breastfeeding continuation after return to work in the European Region.

Methods
Studies published from 2013 to 2023 were collected from Scopus, PubMed, and PsycInfo. Quantitative and qualitative studies published in English or French that explored the association between maternal employment characteristics and any breastfeeding status, duration, or experience were included. Participants included were mothers of healthy children who continued breastfeeding after resuming work. The main determinants were work-related factors that can lead to socially differentiated working conditions, including type of employment (e.g., occupation, employed/self-employed status, type of contract, working time, occupational prestige), working conditions (e.g., work schedule, decision latitude, latitude to organize worktime), and work environment (e.g., occupational exposure, family-friendly workplace policy, social support). The geographic area encompassed countries included in the World Health Organization European Region.

Results
Of the 693 single studies retrieved and screened, 13 were included in the review. Eight studies focused on combining work and breastfeeding, while the others had a broader spectrum by investigating breastfeeding determinants. The represented countries were Spain (n = 4), France (n = 4), UK (n = 2), Ireland (n = 2), and the Netherlands (n = 1). Results highlighted the heterogeneity of measures, time frames, and fields of inquiry, thus revealing a lack of conceptual framework regarding the links between work, breastfeeding, and social health inequalities. Nonetheless, being self-employed, working in a non-manual profession with time flexibility, having lactation rooms at work, being supported by co-workers, and having a breastfeeding workplace policy were salient factors that supported breastfeeding in working mothers.

Conclusions
Supporting working mothers who choose to breastfeed is important given the myriad of adverse factors faced by mothers and their children. These results advocate for targeted actions at the workplace such as time flexibility, breastfeeding facilities, and the promotion of breastfeeding-friendly policies.
Exploring the content and delivery of feedback facilitation co-interventions: a systematic review
Authors: Sykes Michael , Rosenberg-Yunger Zahava R. S. , Quigley Matthew , Gupta Lavanya , Thomas Owen , Robinson Lisa , Caulfield Karen , Ivers Noah , Alderson Sarah 
Published: May 2024

Abstract
Background
Policymakers and researchers recommend supporting the capabilities of feedback recipients to increase the quality of care. There are different ways to support capabilities. We aimed to describe the content and delivery of feedback facilitation interventions delivered alongside audit and feedback within randomised controlled trials.

Methods
We included papers describing feedback facilitation identified by the latest Cochrane review of audit and feedback. The piloted extraction proforma was based upon a framework to describe intervention content, with additional prompts relating to the identification of influences, selection of improvement actions and consideration of priorities and implications. We describe the content and delivery graphically, statistically and narratively.

Results
We reviewed 146 papers describing 104 feedback facilitation interventions. Across included studies, feedback facilitation contained 26 different implementation strategies. There was a median of three implementation strategies per intervention and evidence that the number of strategies per intervention is increasing. Theory was used in 35 trials, although the precise role of theory was poorly described. Ten studies provided a logic model and six of these described their mechanisms of action. Both the exploration of influences and the selection of improvement actions were described in 46 of the feedback facilitation interventions; we describe who undertook this tailoring work. Exploring dose, there was large variation in duration (15–1800 min), frequency (1 to 42 times) and number of recipients per site (1 to 135). There were important gaps in reporting, but some evidence that reporting is improving over time.

Conclusions
Heterogeneity in the design of feedback facilitation needs to be considered when assessing the intervention’s effectiveness. We describe explicit feedback facilitation choices for future intervention developers based upon choices made to date. We found the Expert Recommendations for Implementing Change to be valuable when describing intervention components, with the potential for some minor clarifications in terms and for greater specificity by intervention providers. Reporting demonstrated extensive gaps which hinder both replication and learning. Feedback facilitation providers are recommended to close reporting gaps that hinder replication. Future work should seek to address the ‘opportunity’ for improvement activity, defined as factors that lie outside the individual that make care or improvement behaviour possible.

Review registration
The study protocol was published at: https://www.protocols.io/private/4DA5DE33B68E11ED9EF70A58A9FEAC02.