bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequency of antidepressant use and clinical characteristics of children and adolescents undergoing polysomnography: an observational study
Authors: DelRosso Lourdes M. , Bruni Oliviero , Mogavero Maria P. , Fickensher Amy , Schenck Carlos H. , Ferri Raffaele 
Published: April 2023

Abstract
Background
Antidepressants are increasingly used in children for various psychiatric disorders but also for sleep disorders such as insomnia; however, it is currently unknown how many children undergoing polysomnography (PSG) are taking anti-depressants. The aims were: to determine the frequency of use of antidepressants in paediatric patients referred for PSG, to identify the most common antidepressants used, to investigate the reasons for their use, and to analyse the PSG parameters found in children taking antidepressants.

Method
An observational cross-sectional retrospective chart review of all children undergoing PSG at Seattle Children’s Hospital from 6/14/2020 to 12/8/2022 was carried out. Clinical features (such as diagnosis, especially psychiatric), sleep disorders (such as insomnia and restless sleep), and class of antidepressant used [selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCA), or atypical antidepressants], and PSG parameters were collected for further analysis.

Results
Among 3,371 patients who underwent PSG during the study, 367 children were selected who were taking one antidepressant only (154 boys and 213 girls, mean age was 13.7 ± years 3.69). A significantly decreased sleep stage N3 was found in girls, who were older than boys. Children with insomnia had longer sleep latency than children without, but more N3. There was a prolonged rapid eye movement (REM) sleep latency in children with attention-deficit/hyperactivity disorder and children with autism. REM latency was longer and REM percentage smaller in children taking SNRIs. Periodic leg movement index ≥ 5/hour was found in a higher number of children taking SSRIs or SNRIs (24.9%) than in subjects taking TCA or atypical antidepressants (13.3%) (chi-square 5.29, p = 0.013).

Conclusions
Child and adolescent psychiatrists should question about the effects on sleep (both positive and negative) after initiating therapy with antidepressant medications.
Venetoclax Combined with Azacitidine and Homoharringtonine in Relapsed/Refractory AML: A Multicenter, Phase 2 Trial
Authors: Jin Hua , Zhang Yu , Yu Sijian , Du Xin , Xu Na , Shao Ruoyang , Lin Dongjun , Chen Yanqiu , Xiao Jie , Sun Zhiqiang , Deng Lan , Liang Xinquan , Zhang Hongyu , Guo Ziwen , Dai Min , Shi Pengcheng , Huang Fen , Fan Zhiping , Yin Zhao , Xuan Li , Lin Ren , Jiang Xuejie , Yu Guopan , Liu Qifa 
Published: April 2023

Abstract
Background
Relapsed or refractory acute myeloid leukemia (R/R AML) has a dismal prognosis. The aim of this study was to investigate the activity and tolerability of venetoclax combined with azacitidine plus homoharringtonine (VAH) regimen for R/R AML.

Methods
This phase 2 trial was done at ten hospitals in China. Eligible patients were R/R AML (aged 18–65 years) with an Eastern Cooperative Oncology Group performance status of 0–2. Patients received venetoclax (100 mg on day 1, 200 mg on day 2, and 400 mg on days 3–14) and azacitidine (75 mg/m2 on days 1–7) and homoharringtonine (1 mg/m2 on days 1–7). The primary endpoint was composite complete remission rate [CRc, complete response (CR) plus complete response with incomplete blood count recovery (CRi)] after 2 cycles of treatment. The secondary endpoints include safety and survival.

Results
Between May 27, 2020, and June 16, 2021, we enrolled 96 patients with R/R AML, including 37 primary refractory AML and 59 relapsed AML (16 relapsed after chemotherapy and 43 after allo-HSCT). The CRc rate was 70.8% (95% CI 60.8–79.2). In the patients with CRc, measurable residual disease (MRD)-negative was attained in 58.8% of CRc patients. Accordingly, overall response rate (ORR, CRc plus partial remission (PR)) was 78.1% (95% CI 68.6–85.4). At a median follow-up of 14.7 months (95% CI 6.6–22.8) for all patients, median overall survival (OS) was 22.1 months (95% CI 12.7–Not estimated), and event-free survival (EFS) was 14.3 months (95% CI 7.0–Not estimated). The 1-year OS was 61.5% (95% CI 51.0–70.4), and EFS was 51.0% (95% CI 40.7–60.5). The most common grade 3–4 adverse events were febrile neutropenia (37.4%), sepsis (11.4%), and pneumonia (21.9%).

Conclusions
VAH is a promising and well-tolerated regimen in R/R AML, with high CRc and encouraging survival. Further randomized studies are needed to be explored.
Trial registration clinicaltrials.gov identifier: NCT04424147.
Effects of n-3 PUFA supplementation on oocyte in vitro maturation in mice with polycystic ovary syndrome
Authors: Ma Rujun , Wang Shuxian , Xue Mengqi , Zhang Hong , He Zhaowanyue , Jueraitetibaike Kadiliya , Ge Xie , Chen Li , Yao Bing 
Published: April 2023

Abstractn-3 PUFAs are classic antioxidant that can be used to treat follicular dysplasia and hyperinsulinemia caused by excessive oxidative stress in PCOS women. To investigate the effect of n-3 PUFA supplementation on the oocyte quality of polycystic ovary syndrome (PCOS) mice during in vitro maturation, a PCOS mouse model was established by dehydroepiandrosterone (DHEA). The GV oocytes of the control and PCOS groups were collected and cultured in vitro with or without n-3 PUFAs. After 14 h, the oocytes were collected. Our data demonstrated that the oocyte maturation rate of PCOS mice significantly increased after the addition of 50 µM n-3 PUFAs. The results of immunofluorescence showed that the abnormal rates of spindles and chromosomes in the PCOS + n-3 PUFA group were lower than those in the PCOS group. The mRNA expression of an antioxidant-related gene (Sirt1) and DNA damage repair genes (Brca1/Msh2) was found to be significantly rescued after n-3 treatment. Additionally, the results of living cell staining showed that the addition of n-3 PUFAs could reduce the levels of reactive oxygen species and mitochondrial superoxide in PCOS oocytes. In conclusion, the addition of 50 µM n-3 PUFAs during the in vitro maturation of PCOS mouse oocytes can improve the maturation rate by reducing the level of oxidative stress and the rate of spindle/chromosome abnormalities, providing valuable support during the IVM process.
A novel autophagy-related gene signature associated with prognosis and immune microenvironment in ovarian cancer
Authors: Yang Jiani , Wang Chao , Zhang Yue , Cheng Shanshan , Wu Meixuan , Gu Sijia , Xu Shilin , Wu Yongsong , Wang Yu 
Published: April 2023

AbstractOvarian cancer (OV), the most fatal gynecological malignance worldwide, has high recurrence rates and poor prognosis. Recently, emerging evidence supports that autophagy, a highly regulated multi-step self-digestive process, plays an essential role in OV progression. Accordingly, we filtered 52 potential autophagy-related genes (ATGs) among the 6197 differentially expressed genes (DEGs) identified in TCGA-OV samples (n = 372) and normal controls (n = 180). Based on the LASSO-Cox analysis, we distinguished a 2-gene prognostic signature, namely FOXO1 and CASP8, with promising prognostic value (p-value < 0.001). Together with corresponding clinical features, we constructed a nomogram model for 1-year, 2-year, and 3-year survival, which was validated in both in training (TCGA-OV,p-value < 0.001) and validation (ICGC-OV, p-value = 0.030) cohorts. Interestingly, we evaluated the immune infiltration landscape through the CIBERSORT algorithm, which indicated the upregulation of 5 immune cells, including CD8 + T cells, Tregs, and Macrophages M2, and high expression of critical immune checkpoints (CTLA4, HAVCR2, PDCD1LG2, and TIGIT) in high-risk group. Stepwise, high-risk group exhibited better sensitivity towards chemotherapies of Bleomycin, Sorafenib, Veliparib, and Vinblastine, though less sensitive to immunotherapy. Especially, based on the IHC of tissue microarrays among 125 patients in our institution, we demonstrated that aberrant upregulation of FOXO1 in OV was related to metastasis and poor prognosis. Moreover, FOXO1 could significantly promote tumor invasiveness, migration, and proliferation in OV cell lines, which was assessed through the Transwell, wound-healing, and CCK-8 assay, respectively. Briefly, the autophagy-related signature was a reliable tool to evaluate immune responses and predict prognosis in the realm of OV precision medicine.
G-FORCE: the effectiveness of group psychotherapy for Cluster-C personality disorders: protocol of a pragmatic RCT comparing psychodynamic and two forms of schema group therapy
Authors: van den Heuvel Birre B. , Dekker Jack J. M. , Daniëls M. , Van Henricus L. , Peen Jaap , Bosmans Judith , Arntz Arnoud , Huibers Marcus J. H. 
Published: April 2023

AbstractBackgroundCluster-C personality disorders (PDs), characterized by a high level of fear and anxiety, are related to high levels of distress, societal dysfunctioning and chronicity of various mental health disorders. Evidence for the optimal treatment is extremely scarce. Nevertheless, the need to treat these patients is eminent. In clinical practice, group therapy is one of the frequently offered approaches, with two important frameworks: schema therapy and psychodynamic therapy. These two frameworks suggest different mechanisms of change, but until now, this has not yet been explored. The purpose of the present G-FORCE trial is to find evidence on the differential (cost)effectiveness of two forms of schema group therapy and psychodynamic group therapy in the routine clinical setting of an outpatient clinic and to investigate the underlying working mechanisms and predictors of outcome of these therapies.MethodsIn this mono-centre pragmatic randomized clinical trial, 290 patients with Cluster-C PDs or other specified PD with predominantly Cluster-C traits, will be randomized to one of three treatment conditions: group schema therapy for Cluster-C (GST-C, 1 year), schema-focused group therapy (SFGT, 1.5 year) or psychodynamic group therapy (PG, 2 years). Randomization will be pre-stratified on the type of PD. Change in severity of PD (APD-IV) over 24 months will be the primary outcome measure. Secondary outcome measures are personality functioning, psychiatric symptoms and quality of life. Potential predictors and mediators are selected and measured repeatedly. Also, a cost-effectiveness study will be performed, primarily based on a societal perspective, using both clinical effects and quality-adjusted life years. The time-points of assessment are at baseline, start of treatment and after 1, 3, 6, 9, 12, 18, 24 and 36 months.DiscussionThis study is designed to evaluate the effectiveness and cost-effectiveness of three formats of group psychotherapy for Cluster-C PDs. Additionally, predictors, procedure and process variables are analysed to investigate the working mechanisms of the therapies. This is the first large RCT on group therapy for Cluster-C PDs and will contribute improving the care of this neglected patient group. The absence of a control group can be considered as a limitation.Trial registrationCCMO,NL72826.029.20. Registered on 31 August 2020, first participant included on 18 October 2020.
Caf1 regulates the histone methyltransferase activity of Ash1 by sensing unmodified histone H3
Authors: Yoon Eojin , Song Ji-Joon 
Published: April 2023

AbstractHistone modifications are one of the many key mechanisms that regulate gene expression. Ash1 is a histone H3K36 methyltransferase and is involved in gene activation. Ash1 forms a large complex with Mrg15 and Caf1/p55/Nurf55/RbAp48 (AMC complex). The Ash1 subunit alone exhibits very low activity due to the autoinhibition, and the binding of Mrg15 releases the autoinhibition. Caf1 is a scaffolding protein commonly found in several chromatin modifying complexes and has two histone binding pockets: one for H3 and the other for H4. Caf1 has the ability to sense unmodified histone H3K4 residues using the H3 binding pocket. However, the role of Caf1 in the AMC complex has not been investigated. Here, we dissected the interaction among the AMC complex subunits, revealing that Caf1 uses the histone H4 binding pocket to interact with Ash1 near the histone binding module cluster. Furthermore, we showed that H3K4 methylation inhibits AMC HMTase activity via Caf1 sensing unmodified histone H3K4 to regulate the activity in an internucleosomal manner, suggesting that crosstalk between H3K4 and H3K36 methylation. Our work revealed a delicate mechanism by which the AMC histone H3K36 methyltransferase complex is regulated.
Finerenone attenuates myocardial apoptosis, metabolic disturbance and myocardial fibrosis in type 2 diabetes mellitus
Authors: Jin Tao , Fu Xiangrui , Liu Ming , An Fengshuang 
Published: April 2023

Abstract
Background
Finerenone is a third-generation mineralocorticoid receptor antagonists, which has shown good cardiac function improvement in patients with type 2 diabetes in large-scale clinical trials. However, its specific role in diabetic cardiomyopathy remains unclear. We explored the potential functions and mechanisms of finerenone in diabetic cardiomyopathy.

Methods
The type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin (n = 6, each group). Next the drug group was treated with finerenone (1 mg/kg/day) for 8 weeks. Then we detected the cardiac structure and function and relevant indicators. Neonatal rat cardiomyocytes were used for in vitro culture to determine the direct effect of finerenone on cardiomyocytes stimulated by high glucose and high fatty acid.

Results
Compared with the control group, rats in the type 2 diabetes group exhibited hyperglycemia, hyperlipidemia, and impaired cardiac function. Myocardium showed increased fibrosis and apoptosis. Finerenone attenuated these impairments without changing blood glucose levels. In neonatal rat cardiomyocytes, the stimulation of high concentrations of palmitic acid increased fatty acid uptake, as well as increased reactive oxygen species and apoptosis. Finerenone significantly improved fatty acid metabolism, reduced cellular inflammation levels, and decreased apoptosis.

Conclusions
By blocking the mineralocorticoid receptor, finerenone attenuates cardiac steatosis, myocardial fibrosis and apoptosis, and subsequent myocardial remodeling and diastolic dysfunction in type II diabetic rats.
A study of using epigenetic modulators to enhance response to pembrolizumab (MK-3475) in microsatellite stable advanced colorectal cancer
Authors: Baretti Marina , Murphy Adrian G. , Zahurak Marianna , Gianino Nicole , Parkinson Rose , Walker Rosalind , Lopez-Vidal Tamara Y. , Zheng Lei , Rosner Gary , Ahuja Nita , Kurt Schalper , Azad Nilofer S. 
Published: April 2023

Abstract
Background
Approximately 95% of advanced colorectal cancer patients (CRC) have mismatch repair MMR-proficient (MMRp) tumors, which do not respond to PD1 blockade alone. Preclinical studies have shown that combined histone deacetylases (HDAC) and/or DNA methyltransferases (DNMT) inhibition can induce susceptibility to immune checkpoint therapy and inhibit tumor growth. We conducted a pilot trial evaluating PD-1 immune checkpoint inhibitor therapy in combination with DNMT and HDAC inhibitors in MMRp CRC. The study was designed with a biological endpoint of change in immune cell infiltration, to determine the optimal epigenetic combination that optimizes the tumor microenvironment. This trial was designed to test that hypothesis.

Results
From January 2016 to November 2018, 27 patients were enrolled with median age of 57 (range 40–69) years. Median progression-free survival and overall survival were 2.79 months and 9.17, respectively. One patient in Arm C achieved a durable partial response by RECIST criteria, lasting for approximately 19 months. The most common treatment-related hematological adverse events in all arms were anemia (62%), lymphopenia (54%) and thrombocytopenia (35%), and non-hematological AEs were anorexia (65%), nausea (77%), and vomiting (73%).

Conclusions
The combination of 5-azacitidine and romidepsin with pembrolizumab was safe and tolerable in patients with advanced MMRp CRC, but with a minimal activity. Further mechanistic investigations are needed to understand epigenetic-induced immunologic shift and to expand the potential applicability of checkpoint inhibitors in this setting.
Characterization of molecular subtypes based on chromatin regulators and identification of the role of NPAS2 in lung adenocarcinoma
Authors: Huang Yongbiao , Xiao Lingyan , Daba Motuma Yigezu , Xu Duo , Wang Yuan , Li Long , Li Qian , Liu Bo , Qin Wan , Zhang Huixian , Yuan Xianglin 
Published: April 2023

Abstract
Background
Chromatin regulators (CRs) are critical epigenetic modifiers and have been reported to play critical roles during the progression of various tumors, but their role in lung adenocarcinoma (LUAD) has not been comprehensively studied.

Methods
Differential expression and univariate Cox regression analyses were conducted to identify the prognostic CRs. Consensus clustering was applied to classify the subtypes of LUAD based on prognostic CRs. LASSO-multivariate Cox regression method was used for construction of a prognostic signature and development of chromatin regulator-related gene index (CRGI). The capacity of CRGI to distinguish survival was evaluated via Kaplan–Meier method in multiple datasets. Relationship between CRGI and tumor microenvironment (TME) was evaluated. Additionally, clinical variables and CRGI were incorporated to create a nomogram. The role of the prognostic gene NPAS2 in LUAD was elucidated via clinical samples validation and a series of in vitro and in vivo experiments.

Results
Two subtypes of LUAD were classified based on 46 prognostic CRs via consensus clustering which had significantly different survival and TME. A prognostic signature consisting of six CRs (MOCS, PBK, CBX3, A1CF, NPAS2, and CTCFL) was developed and proved to be an effective survival predictor in multiple independent datasets. The prognostic signature was also demonstrated to be an indicator of TME and sensitivity to immunotherapy and chemotherapy. The nomogram was suggested to be a simple tool that can predict survival accurately. Clinical samples show that NPAS2 is highly expressed in LUAD tissues, and in vitro and in vivo experiments demonstrated that inhibition of NPAS2 impeded malignant progression of LUAD cells.

Conclusions
Our study comprehensively unveiled the functions of CRs in LUAD, developed a classifier to predict survival and response to treatments, and suggested that NPAS2 promoted LUAD progression for the first time.
Metabolic engineering of Bacillus subtilis toward the efficient and stable production of C30-carotenoids
Authors: Filluelo Oriana , Ferrando Jordi , Picart Pere 
Published: April 2023

AbstractCommercial carotenoid production is dominated by chemical synthesis and plant extraction, both of which are unsustainable and can be detrimental to the environment. A promising alternative for the mass production of carotenoids from both an ecological and commercial perspective is microbial synthesis. To date, C30 carotenoid production in Bacillus subtilis has been achieved using plasmid systems for the overexpression of biosynthetic enzymes. In the present study, we employed a clustered regularly interspaced short palindromic repeat-Cas9 (CRISPR-Cas9) system to develop an efficient, safe, and stable C30 carotenoid-producing B. subtilis strain, devoid of plasmids and antibiotic selection markers. To this end, the expression levels of crtM (dehydrosqualene synthase) and crtN (dehydrosqualene desaturase) genes from Staphylococcus aureus were upregulated by the insertion of three gene copies into the chromosome of B. subtilis. Subsequently, the supply of the C30 carotenoid precursor farnesyl diphosphate (FPP), which is the substrate for CrtMN enzymes, was enhanced by expressing chromosomally integrated Bacillus megaterium-derived farnesyl diphosphate synthase (FPPS), a key enzyme in the FPP pathway, and abolishing the expression of farnesyl diphosphate phosphatase (YisP), an enzyme responsible for the undesired conversion of FPP to farnesol. The consecutive combination of these features resulted in a stepwise increased production of C30 carotenoids. For the first time, a B. subtilis strain that can endogenously produce C30 carotenoids has been constructed, which we anticipate will serve as a chassis for further metabolic engineering and fermentation optimization aimed at developing a commercial scale bioproduction process.
Bile acid-mediated signaling in cholestatic liver diseases
Authors: Zeng Jing , Fan Jiangao , Zhou Huiping 
Published: April 2023

AbstractChronic cholestatic liver diseases, such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), are associated with bile stasis and gradually progress to fibrosis, cirrhosis, and liver failure, which requires liver transplantation. Although ursodeoxycholic acid is effective in slowing the disease progression of PBC, it has limited efficacy in PSC patients. It is challenging to develop effective therapeutic agents due to the limited understanding of disease pathogenesis. During the last decade, numerous studies have demonstrated that disruption of bile acid (BA) metabolism and intrahepatic circulation promotes the progression of cholestatic liver diseases. BAs not only play an essential role in nutrition absorption as detergents but also play an important role in regulating hepatic metabolism and modulating immune responses as key signaling molecules. Several excellent papers have recently reviewed the role of BAs in metabolic liver diseases. This review focuses on BA-mediated signaling in cholestatic liver disease.
The use of text-mining software to facilitate screening of literature on centredness in health care
Authors: Forsgren Emma , Wallström Sara , Feldthusen Caroline , Zechner Niklas , Sawatzky Richard , Öhlén Joakim 
Published: April 2023

AbstractResearch evidence supporting the implementation of centredness in health care is not easily accessible due to the sheer amount of literature available and the diversity in terminology and conceptualisations used. The use of text-mining functions to semi-automate the process of screening and collating citations for a review is a way of tackling the vast amount of research citations available today. There are several programmes that use text-mining functions to facilitate screening and data extraction for systematic reviews. However, the suitability of these programmes for reviews on broad topics of research, as well as the general uptake by researchers, is unclear. This commentary has a dual aim, which consists in outlining the challenges of screening literature in fields characterised by vague and overlapping conceptualisations, and to exemplify this by exploratory use of text-mining in the context of a scoping review on centredness in health care.