bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of frailty status on clinical and functional outcomes after concomitant valve replacement and bipolar radiofrequency ablation in patients aged 65 years and older
Authors: Lin Zhi-qin , Chen Xiu-jun , Dai Xiao-fu , Chen Liang-wan , Lin Feng 
Published: November 2022

Abstract
Background
To evaluate the prognostic value of frailty in older recipients of concomitant valve replacement (VR) and bipolar radiofrequency ablation (BRFA), we examined whether clinical and functional outcomes differed between frail and non-frail groups of older patients referred for concomitant VR and BRFA.

Methods
In a single-center retrospective observational cohort study, we compared the clinical and functional outcomes in frail versus non-frail patients. Frailty was assessed using the 5-item Cardiovascular Health Study (CHS) frailty scale. Patients were divided into two groups, frail and non-frail. Functional outcome was assessed using the internationally validated Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) questionnaire.

Results
We enrolled 185 patients aged ≥ 65 years who underwent concomitant VR and BRFA. About 36.2% (n = 67) of the patients were included in the frail group and the remaining patients (n = 118) in the non-frail group. Follow-up was complete with a median duration of 58 months (interquartile range 44–76 months). Significant differences were observed between the two groups with respect to postoperative pulmonary complications (frail vs. non-frail patients, 50.74% vs. 22.9%, respectively, P < .001) and hospital mortality (10.45% vs. 1.69%, respectively, P = .021). The frail group had a higher adjusted risk for all-cause mortality (adjusted HR 4.06; 95% CI 1.33 to 12.38; P = .014) and all-cause hospitalization (adjusted HR 2.24; 95% CI 1.12 to 4.50; P = .023). Frailty was associated with lower overall AFEQT scores at baseline (Estimate, − 0.400; 95% CI − 0.532 to − 0.267; P < .001). Compared to the non-frail group, the frail group continued to have lower overall AFEQT scores with no significant improvement in follow-up at 1 year and 2 years after concomitant VR and BRFA.

Conclusion
Frail patients had lower baseline AFEQT scores and were more likely to have adverse outcomes from postoperative pulmonary complications, and frailty was also an independent risk factor for long-term all-cause mortality and all-cause rehospitalization. Further studies are needed to assess the impact of frailty.
Has the “Double Reduction” policy relieved stress? A follow-up study on Chinese adolescents
Authors: Wang Dongfang , Chen Xiao-Yan , Ma Zijuan , Liu Xianchen , Fan Fang 
Published: November 2022

Abstract
Purpose
“Double Reduction” Policy requires schools to reduce the burden of excessive homework and off-campus training for Chinese students to reduce their academic stress and promote mental health. We conducted a study in compulsory education students before and after the “Double Reduction” Policy to explore changes in mental health problems and relevant influential factors.

Methods
A total of 28,398 elementary and junior high school students completed both waves of the survey through electronic questionnaires. Depressive symptoms were assessed using the Patient Heath Questionnaire (PHQ-9), and anxiety symptoms were assessed using the Generalized Anxiety Disorder Scale (GDA-7). Demographic information was evaluated at baseline, and “Double Reduction” related factors and negative life events were measured at follow up.

Results
The overall depression and anxiety levels significantly decreased after the “Double Reduction” Policy. Girls, poor parental marital quality, chronic physical illness, and psychiatric family history were related to increased occurrence of mental health. Sleep duration > 8 h/night, reduced homework, more extracurricular activities more time with parents, and reduced academic stress were protective factors against mental health problems.

Conclusions
The “Double Reduction” Policy has improved the mental health symptoms of students to a certain extent. Appropriately increasing sleep time, participating in more extracurricular activities and parental involvement, and reducing the burden of homework are effective ways to promote the development of students’ mental health.
Pre-exposure prophylaxis with tixagevimab/cilgavimab (AZD7442) prevents severe SARS-CoV-2 infection in recipients of allogeneic hematopoietic stem cell transplantation during the Omicron wave: a multicentric retrospective study of SFGM-TC
Authors: Jondreville Ludovic , D’Aveni Maud , Labussière-Wallet Hélène , Le Bourgeois Amandine , Villate Alban , Berceanu Ana , Bezsera Silvia-Maria , Thiebaut Anne , Boissard-Simonet Marion , Legrand Marlène , Cornillon Jérôme , Rubio Marie-Thérèse , Chevallier Patrice , Nguyen Stéphanie 
Published: November 2022

AbstractSince the emergence of the Omicron variant of SARS-CoV-2, though considered less virulent, hospitalization and death rates among immunocompromised patients remain high, especially for poor responders to vaccination. We conducted a retrospective multicentric study to evaluate pre-exposure prophylaxis with AZD7442 (tixagevimab/cilgavimab) for preventing COVID-19 in adult allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. Among the 161 patients of our cohort, 22 (14%) contracted COVID-19 after a median follow-up of 105 days, but no severe form was observed. Only one major adverse event was reported: an acute coronary syndrome, resolved without sequelae. Pending randomized controlled trial results, our data support the use of AZD7442 as pre-exposure prophylaxis for COVID-19 during Omicron wave in allo-HSCT patients who failed to develop humoral immunity to vaccination, to prevent severe and potentially lethal forms of SARS-CoV-2 infection.
Crenigacestat blocking notch pathway reduces liver fibrosis in the surrounding ecosystem of intrahepatic CCA viaTGF-β inhibition
Authors: Mancarella Serena , Gigante Isabella , Serino Grazia , Pizzuto Elena , Dituri Francesco , Valentini Maria F. , Wang Jingxiao , Chen Xin , Armentano Raffaele , Calvisi Diego F. , Giannelli Gianluigi 
Published: November 2022

Abstract
Background
Intrahepatic cholangiocarcinoma (iCCA) is a highly malignant tumor characterized by an intensive desmoplastic reaction due to the exaggerated presence of the extracellular (ECM) matrix components. Liver fibroblasts close to the tumor, activated by transforming growth factor (TGF)-β1 and expressing high levels of α-smooth muscle actin (α-SMA), become cancer-associated fibroblasts (CAFs). CAFs are deputed to produce and secrete ECM components and crosstalk with cancer cells favoring tumor progression and resistance to therapy. Overexpression of Notch signaling is implicated in CCA development and growth. The study aimed to determine the effectiveness of the Notch inhibitor, Crenigacestat, on the surrounding microenvironment of iCCA.

Methods
We investigated Crenigacestat’s effectiveness in a PDX model of iCCA and human primary culture of CAFs isolated from patients with iCCA.

Results
In silico analysis of transcriptomic profiling from PDX iCCA tissues treated with Crenigacestat highlighted “liver fibrosis” as one of the most modulated pathways. In the iCCA PDX model, Crenigacestat treatment significantly (p < 0.001) reduced peritumoral liver fibrosis. Similar results were obtained in a hydrodynamic model of iCCA. Bioinformatic prediction of the upstream regulators related to liver fibrosis in the iCCA PDX treated with Crenigacestat revealed the involvement of the TGF-β1 pathway as a master regulator gene showing a robust connection between TGF-β1 and Notch pathways. Consistently, drug treatment significantly (p < 0.05) reduced TGF-β1 mRNA and protein levels in tumoral tissue. In PDX tissues, Crenigacestat remarkably inhibited TGF-β signaling and extracellular matrix protein gene expression and reduced α-SMA expression. Furthermore, Crenigacestat synergistically increased Gemcitabine effectiveness in the iCCA PDX model. In 31 iCCA patients, TGF-β1 and α-SMA were upregulated in the tumoral compared with peritumoral tissues. In freshly isolated CAFs from patients with iCCA, Crenigacestat significantly (p < 0.001) inhibited Notch signaling, TGF-β1 secretion, and Smad-2 activation. Consequently, Crenigacestat also inactivated CAFs reducing (p < 0.001) α-SMA expression. Finally, CAFs treated with Crenigacestat produced less (p < 005) ECM components such as fibronectin, collagen 1A1, and collagen 1A2.

Conclusions
Notch signaling inhibition reduces the peritumoral desmoplastic reaction in iCCA, blocking the TGF-β1 canonical pathway.
Systematized and efficient: organization of critical care in the future
Authors: Esper Annette M. , Arabi Yaseen M. , Cecconi Maurizio , Du Bin , Giamarellos-Bourboulis Evangelos J. , Juffermans Nicole , Machado Flavia , Peake Sandra , Phua Jason , Rowan Kathryn , Suh Gee Young , Martin Greg S. 
Published: November 2022

AbstractSince the advent of critical care in the twentieth century, the core elements that are the foundation for critical care systems, namely to care for critically ill and injured patients and to save lives, have evolved enormously. The past half-century has seen dramatic advancements in diagnostic, organ support, and treatment modalities in critical care, with further improvements now needed to achieve personalized critical care of the highest quality. For critical care to be even higher quality in the future, advancements in the following areas are key: the physical ICU space; the people that care for critically ill patients; the equipment and technologies; the information systems and data; and the research systems that impact critically ill patients and families. With acutely and critically ill patients and their families as the absolute focal point, advancements across these areas will hopefully transform care and outcomes over the coming years.
Cross-regulome profiling of RNA polymerases highlights the regulatory role of polymerase III on mRNA transcription by maintaining local chromatin architecture
Authors: Jiang Yongpeng , Huang Jie , Tian Kai , Yi Xiao , Zheng Haonan , Zhu Yi , Guo Tiannan , Ji Xiong 
Published: November 2022

Abstract
Background
Mammalian cells have three types of RNA polymerases (Pols), Pol I, II, and III. However, the extent to which these polymerases are cross-regulated and the underlying mechanisms remain unclear.

Results
We employ genome-wide profiling after acute depletion of Pol I, Pol II, or Pol III to assess cross-regulatory effects between these Pols. We find that these enzymes mainly affect the transcription of their own target genes, while certain genes are transcribed by the other polymerases. Importantly, the most active type of crosstalk is exemplified by the fact that Pol III depletion affects Pol II transcription. Pol II genes with transcription changes upon Pol III depletion are enriched in diverse cellular functions, and Pol III binding sites are found near their promoters. However, these Pol III binding sites do not correspond to transfer RNAs. Moreover, we demonstrate that Pol III regulates Pol II transcription and chromatin binding of the facilitates chromatin transcription (FACT) complex to alter local chromatin structures, which in turn affects the Pol II transcription rate.

Conclusions
Our results support a model suggesting that RNA polymerases show cross-regulatory effects: Pol III affects local chromatin structures and the FACT-Pol II axis to regulate the Pol II transcription rate at certain gene loci. This study provides a new perspective for understanding the dysregulation of Pol III in various tissues affected by developmental diseases.
Phytochemical analysis and anticholinesterase activity of aril of Myristica fragrans Houtt
Authors: Rastegari Arezoo , Manayi Azadeh , Rezakazemi Mahdi , Eftekhari Mahdieh , Khanavi Mahnaz , Akbarzadeh Tahmineh , Saeedi Mina 
Published: November 2022

AbstractIn this study, the ethyl acetate fraction of Myristica fragrans Houtt. was investigated for its in vitro anticholinesterase activity as well as neuroprotectivity against H2O2-induced cell death in PC12 neuronal cells and the ability to chelate bio-metals (Zn2+, Fe2+, and Cu2+). The fraction was inactive toward acetylcholinesterase (AChE); however, it inhibited the butyrylcholinesterase (BChE) with IC50 value of 68.16 µg/mL, compared with donepezil as the reference drug (IC50 = 1.97 µg/mL) via Ellman’s method. It also showed good percentage of neuroprotection (86.28% at 100 µg/mL) against H2O2-induced neurotoxicity and moderate metal chelating ability toward Zn2+, Fe2+, and Cu2+. The phytochemical study led to isolation and identification of malabaricone A (1), malabaricone C (2), 4-(4-(3,4-dimethoxyphenyl)-2,3-dimethylbutyl)benzene-1,2-diol (3), nectandrin B (4), macelignan (5), and 4-(4-(benzo[d][1,3]dioxol-5-yl)-1-methoxy-2,3-dimethylbutyl)-2-methoxyphenol (6) which were assayed for their cholinesterase (ChE) inhibitory activity. Compounds 1 and 3 were not previously reported for M. fragrans. Among isolated compounds, compound 2 showed the best activity toward both AChE and BChE with IC50 values of 25.02 and 22.36 μM, respectively, compared with donepezil (0.07 and 4.73 μM, respectively).
An examination of mediation by DNA methylation on birthweight differences induced by assisted reproductive technologies
Authors: Carlsen Ellen Ø. , Lee Yunsung , Magnus Per , Jugessur Astanand , Page Christian M. , Nustad Haakon E. , Håberg Siri E. , Lie Rolv T. , Magnus Maria C. 
Published: November 2022

AbstractBackgroundChildren born after assisted reproductive technologies (ART) differ in birthweight from those naturally conceived. It has been hypothesized that this might be explained by epigenetic mechanisms. We examined whether cord blood DNA methylation mediated the birthweight difference between 890 newborns conceived by ART (764 by fresh embryo transfer and 126 frozen thawed embryo transfer) and 983 naturally conceived newborns from the Norwegian Mother, Father, and Child Cohort Study (MoBa). DNA methylation was measured by the Illumina Infinium MethylationEPIC array. We conducted mediation analyses to assess whether differentially methylated CpGs mediated the differences in birthweight observed between: (1) fresh embryo transfer and natural conception and (2) frozen and fresh embryo transfer.ResultsWe observed a difference in birthweight between fresh embryo transfer and naturally conceived offspring of − 120 g. 44% (95% confidence interval [CI] 26% to 81%) of this difference in birthweight between fresh embryo transfer and naturally conceived offspring was explained by differences in methylation levels at four CpGs nearLOXL1,CDH20, andDRC1. DNA methylation differences at two CpGs nearPTGS1andRASGRP4jointly mediated 22% (95% CI 8.1% to 50.3%) of the birthweight differences between fresh and frozen embryo transfer.ConclusionOur findings suggest that DNA methylation is an important mechanism in explaining birthweight differences according to the mode of conception. Further research should examine how gene regulation at these loci influences fetal growth.
Gene body methylation in cancer: molecular mechanisms and clinical applications
Authors: Wang Qi , Xiong Fei , Wu Guanhua , Liu Wenzheng , Chen Junsheng , Wang Bing , Chen Yongjun 
Published: November 2022

AbstractDNA methylation is an important epigenetic mechanism that regulates gene expression. To date, most DNA methylation studies have focussed on CpG islands in the gene promoter region, and the mechanism of methylation and the regulation of gene expression after methylation have been clearly elucidated. However, genome-wide methylation studies have shown that DNA methylation is widespread not only in promoters but also in gene bodies. Gene body methylation is widely involved in the expression regulation of many genes and is closely related to the occurrence and progression of malignant tumours. This review focusses on the formation of gene body methylation patterns, its regulation of transcription, and its relationship with tumours, providing clues to explore the mechanism of gene body methylation in regulating gene transcription and its significance and application in the field of oncology.
On the shape-preserving properties of λ-Bernstein operators
Authors: Su Lian-Ta , Mutlu Gökhan , Çekim Bayram 
Published: November 2022

AbstractWe investigate the shape-preserving properties of λ-Bernstein operators $B_{n,\lambda } ( f;x ) $

B

n
,
λ

(
f
;
x
)
that were recently introduced Bernstein-type operators defined by a new Beziér basis with shape parameter $\lambda \in [ -1,1 ] $
λ
∈
[
−
1
,
1
]
. For this purpose, we express $B_{n,\lambda } ( f;x ) $

B

n
,
λ

(
f
;
x
)
as a sum of a classical Bernstein operator and a sum of first order divided differences of f. Using this new representation, we prove that $B_{n,\lambda } ( f;x ) $

B

n
,
λ

(
f
;
x
)
preserves monotonic functions for all $\lambda \in [ -1,1 ] $
λ
∈
[
−
1
,
1
]
. However, we show by a counter example that $B_{n,\lambda } ( f;x ) $

B

n
,
λ

(
f
;
x
)
does not preserve convex functions for some $\lambda \in [ -1,1 ] $
λ
∈
[
−
1
,
1
]
. We present a weaker result for the case $\lambda \in [ 0,1 ] $
λ
∈
[
0
,
1
]
for a special class of functions. Finally, we analyze the monotonicity of λ-Bernstein operators with n and show that $B_{n,\lambda } ( f;x ) $

B

n
,
λ

(
f
;
x
)
is not monotonic with n for some λ if $1/2 <\lambda \leq 1$
1
/
2
<
λ
≤
1
.
The integration of large-scale public data and network analysis uncovers molecular characteristics of psoriasis
Authors: Federico Antonio , Pavel Alisa , Möbus Lena , McKean David , del Giudice Giusy , Fortino Vittorio , Niehues Hanna , Rastrick Joe , Eyerich Kilian , Eyerich Stefanie , van den Bogaard Ellen , Smith Catherine , Weidinger Stephan , de Rinaldis Emanuele , Greco Dario 
Published: November 2022

AbstractIn recent years, a growing interest in the characterization of the molecular basis of psoriasis has been observed. However, despite the availability of a large amount of molecular data, many pathogenic mechanisms of psoriasis are still poorly understood. In this study, we performed an integrated analysis of 23 public transcriptomic datasets encompassing both lesional and uninvolved skin samples from psoriasis patients. We defined comprehensive gene co-expression network models of psoriatic lesions and uninvolved skin. Moreover, we curated and exploited a wide range of functional information from multiple public sources in order to systematically annotate the inferred networks. The integrated analysis of transcriptomics data and co-expression networks highlighted genes that are frequently dysregulated and show aberrant patterns of connectivity in the psoriatic lesion compared with the unaffected skin. Our approach allowed us to also identify plausible, previously unknown, actors in the expression of the psoriasis phenotype. Finally, we characterized communities of co-expressed genes associated with relevant molecular functions and expression signatures of specific immune cell types associated with the psoriasis lesion. Overall, integrating experimental driven results with curated functional information from public repositories represents an efficient approach to empower knowledge generation about psoriasis and may be applicable to other complex diseases.
Dating app usage and motivations for dating app usage are associated with increased disordered eating
Authors: Blake K. , Portingale J. , Giles S. , Griffiths S. , Krug I. 
Published: November 2022

AbstractThe centrality of physical appearance in dating app environments may constitute an appearance-related pressure that increases the likelihood of body dissatisfaction (BD) and disordered eating (DE), thus exacerbating the relationship between DE-predictive traits and DE itself. Although dating app use has been linked to BD and DE, prior research has also neglected the role of individuals’ dating app use motivations and relevant traits in eating pathology. To address these gaps, the current study investigated whether dating app usage moderated the effects of appearance-based rejection sensitivity, fear of negative evaluation, emotion dysregulation, and perceived social rank on DE. We also examined the unique effects of individuals’ dating app use motivations on DE. Participants (N = 690) completed baseline measures of demographic and trait variables including dating app usage. DE was positively associated with female gender, higher body mass index, a history of eating disorder (ED) diagnosis, appearance-based rejection sensitivity, and emotion dysregulation. There was a small, positive association between dating app usage and DE, indicating that dating app users were more likely to report DE symptoms, appearance-based rejection sensitivity, and emotion dysregulation. No investigated predictor was moderated by dating app usage, but four of the six measured motivations for using dating apps (love, self-worth, ease of communication, and thrill of excitement motivations) were associated with DE among the dating app user sample (casual sex and trendiness motivations were not). Given that DE behaviours can lead to EDs, the present findings suggest that lifetime dating app usage may increase socio-cultural appearance pressures that confer risk for DE.
Facebook use intensity and depressive symptoms: a moderated mediation model of problematic Facebook use, age, neuroticism, and extraversion
Authors: Gugushvili Nino , Täht Karin , Ruiter Robert A. C. , Verduyn Philippe 
Published: November 2022

Abstract
Background
Research on the relationship between Facebook use intensity and depressive symptoms has resulted in mixed findings. In contrast, problematic Facebook use has been found to be a robust predictor of depressive symptoms. This suggests that when intense Facebook use results in a problematic usage pattern, it may indirectly predict depressive symptoms. However, this mediation pathway has never been examined. Moreover, it remains unclear whether the possible indirect relationship between Facebook use intensity and depressive symptoms through problematic Facebook use is moderated by demographic (age), and personality (neuroticism and extraversion) characteristics.

Methods
To address these gaps, we conducted an online cross-sectional study (n = 210, 55% female, age range: 18–70 years old, Mage = 30.26, SD = 12.25). We measured Facebook use intensity (Facebook Intensity Scale), problematic Facebook use (Bergen Facebook Addiction Scale), depressive symptoms (Center for Epidemiologic Studies Depression Scale Revised), and neuroticism and extraversion (Ten Item Personality Inventory).

Results
A mediation analysis revealed that problematic Facebook use fully mediates the relationship between Facebook use intensity and depressive symptoms. Moreover, a moderated mediation analysis demonstrated that this indirect relationship is especially strong among young users and users scoring high on neuroticism.

Conclusions
These findings expand our understanding of the mechanisms underlying the relationship between Facebook use intensity and depressive symptoms and describe user characteristics that act as vulnerability factors in this relationship.