bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laboratory methods to decipher epigenetic signatures: a comparative review
Authors: Halabian Raheleh , Valizadeh Arshad  , Ahmadi Ali , Saeedi Pardis , Azimzadeh Jamalkandi Sadegh , Alivand Mohammad Reza 
Published: November 2021

AbstractEpigenetics refers to nucleotide sequence-independent events, and heritable changes, including DNA methylation and histone modification (as the two main processes), contributing to the phenotypic features of the cell. Both genetics and epigenetics contribute to determining the outcome of regulatory gene expression systems. Indeed, the flexibility of epigenetic effects and stability of genetic coding lead to gene regulation complexity in response signals. Since some epigenetic changes are significant in abnormalities such as cancers and neurodegenerative diseases, the initial changes, dynamic and reversible properties, and diagnostic potential of epigenomic phenomena are subject to epigenome-wide association studies (EWAS) for therapeutic aims. Based on recent studies, methodological developments are necessary to improve epigenetic research. As a result, several methods have been developed to explore epigenetic alterations at low, medium, and high scales, focusing on DNA methylation and histone modification detection. In this research field, bisulfite-, enzyme sensitivity- and antibody specificity-based techniques are used for DNA methylation, whereas histone modifications are gained based on antibody recognition. This review provides a mechanism-based understanding and comparative overview of the most common techniques for detecting the status of epigenetic effects, including DNA methylation and histone modifications, for applicable approaches from low- to high-throughput scales.
Integration of adeno-associated virus (AAV) into the genomes of most Thai and Mongolian liver cancer patients does not induce oncogenesis
Authors: Schäffer Alejandro A. , Dominguez Dana A. , Chapman Lesley M. , Gertz E. Michael , Budhu Anuradha , Forgues Marshonna , Chaisaingmongkol Jittiporn , Rabibhadana Siritida , Pupacdi Benjarath , Wu Xiaolin , Bayarsaikhan Enkhjargal , Harris Curtis C. , Ruchirawat Mathuros , Ruppin Eytan , Wang Xin Wei 
Published: November 2021

AbstractBackgroundEngineered versions of adeno-associated virus (AAV) are commonly used in gene therapy but evidence revealing a potential oncogenic role of natural AAV in hepatocellular carcinoma (HCC) has raised concerns. The frequency of potentially oncogenic integrations has been reported in only a few populations. AAV infection and host genome integration in another type of liver cancer, cholangiocarcinoma (CCA), has been studied only in one cohort. All reported oncogenic AAV integrations in HCC come from strains resembling the fully sequenced AAV2 and partly sequenced AAV13. When AAV integration occurs, only a fragment of the AAV genome is detectable in later DNA or RNA sequencing. The integrated fragment is typically from the 3’ end of the AAV genome, and this positional bias has been only partly explained. Three research groups searched for evidence of AAV integration in HCC RNAseq samples in the Cancer Genome Atlas (TCGA) but reported conflicting results.ResultsWe collected and analyzed whole transcriptome and viral capture DNA sequencing in paired tumor and non-tumor samples from two liver cancer Asian cohorts from Thailand (N = 147, 47 HCC and 100 intrahepatic cholangiocarcinoma (iCCA)) and Mongolia (N = 70, all HCC). We found only one HCC patient with a potentially oncogenic integration of AAV, in contrast to higher frequency reported in European patients. There were no oncogenic AAV integrations in iCCA patients. AAV genomic segments are present preferentially in the non-tumor samples of Thai patients.By analyzing the AAV genome positions of oncogenic and non-oncogenic integrated fragments, we found that almost all the putative oncogenic integrations overlap the X gene, which is present and functional only in the strain AAV2 among all fully sequenced strains. This gene content difference could explain why putative oncogenic integrations from other AAV strains have not been reported.We resolved the discrepancies in previous analyses of AAV presence in TCGA HCC samples and extended it to CCA. There are 12 TCGA samples with an AAV segment and none are in Asian patients. AAV segments are present in preferentially in TCGA non-tumor samples, like what we observed in the Thai patients.ConclusionsOur findings suggest a minimal AAV risk of hepatocarcinogenesis in Asian liver cancer patients. The partial genome presence and positional bias of AAV integrations into the human genome has complicated analysis of possible roles of AAV in liver cancer.
Oxytocin administration for induction and augmentation of labour in polish maternity units – an observational study
Authors: Baranowska Barbara , Kajdy Anna , Kiersnowska Iwona , Sys Dorota , Tataj-Puzyna Urszula , Daly Déirdre , Rabijewski Michał , Bączek Grażyna , Węgrzynowska Maria 
Published: November 2021

AbstractBackgroundThere is not enough data regarding practices and protocols on the dose of oxytocin administrated to women during labour. Empirical evidence indicates that compliance with the guidelines improves the quality of healthcare and reduces adverse effects. The study aimed to evaluate practices of oxytocin provision for labour induction and augmentation in two maternity units in Poland.MethodsThe article presents a prospective observational study. Data from 545 (n = 545) labours was collected in two maternity units. First, the total dose (the total amount of oxytocin provided from the beginning in the labour ward until delivery including the III and IV stage of labour) and cumulative dose of oxytocin (the amount of oxytocin given until the birth of the neonate) administered to women during labour was calculated. Then, the relationship between the cumulative dose of oxytocin and short term perinatal outcomes (mode of delivery, use of epidural anaesthesia, Apgar scores, birth weight and postpartum blood loss) was analysed. Finally, the compliance of oxytocin supply during labour with national guidelines in the following five criteria: medium, start dose, escalation rate, interval, the continuation of infusion after established labour was examined.ResultsThe average cumulative dose of oxytocin administrated to women before birth was 4402 mU following labour induction and 2366 mU following labour augmentation. The actual administration of oxytocin deviated both from the unit and national guidelines in 93.6% of all observed labours (mainly because of continuation of infusion after established labour). We found no statistically significant correlation between the cumulative dose of oxytocin administered and mode of delivery, immediate postpartum blood loss or Apgar scores. There was no observed effect of cumulative dose oxytocin on short-term perinatal outcomes. The two units participating in the study had similar protocols and did not differ significantly in terms of total oxytocin dose, rates of induction and augmentation - the only observed difference was the mode of delivery.ConclusionsThe study showed no effect of the mean cumulative oxytocin dose on short-term perinatal outcomes and high rate of non-compliance of the practice of oxytocin administration for labour induction and augmentation with the national recommendations. Cooperation between different professional groups of maternity care providers should be considered in building national guidelines for maternity care.. Further studies investigating possible long-term effects of the meant cumulative dose of oxytocin and the reasons for non-compliance of practice with guidelines should be carried out.
Construction of a microenvironment immune gene model for predicting the prognosis of endometrial cancer
Authors: Wang Yichen , Zhang Jingkai , Zhou Yijun , Li Zhiguang , Lv Dekang , Liu Quentin 
Published: November 2021

Abstract
Background
Infiltrating immune and stromal cells are important components of the endometrial cancer (EC) microenvironment, which has a significant effect on the biological behavior of EC, suggesting that unique immune-related genes may be associated with the prognosis of EC. However, the association of immune-related genes with the prognosis of EC has not been elucidated. We attempted to identify immune-related genes with potentially prognostic value in EC using The Cancer Genome Atlas database and the relationship between immune microenvironment and EC.

Methods
We analyzed 578 EC samples from TCGA database and used weighted gene co-expression network analysis to screen out immune-related genes. We constructed a protein–protein interaction network and analyzed it using STRING and Cytoscape. Immune-related genes were analyzed through conjoint Cox regression and random forest algorithm analysis were to identify a multi-gene prediction model and stratify low-risk and high-risk groups of EC patients. Based on these data, we constructed a nomogram prediction model to improve prognosis assessment. Evaluation of Immunological, gene mutations and gene enrichment analysis were applied on these groups to quantify additional differences.

Results
Using conjoint Cox regression and random forest algorithm, we found that TRBC2, TRAC, LPXN, and ARHGAP30 were associated with the prognosis of EC and constructed four gene risk models for overall survival and a consistent nomogram. The time-dependent receiver operating characteristic curve analysis revealed that the area under the curve for 1-, 3-, and 5-y overall survival was 0.687, 0.699, and 0.76, respectively. These results were validated using a validation cohort. Immune-related pathways were mostly enriched in the low-risk group, which had higher levels of immune infiltration and immune status.

Conclusion
Our study provides new insights for novel biomarkers and immunotherapy targets in EC.
Co-design of a digital dietary intervention for adults at risk of type 2 diabetes
Authors: Tay Brenda S. J. , Edney Sarah M. , Brinkworth Grant D. , Cox David N. , Wiggins Bonnie , Davis Aaron , Gwilt Ian , Haveman-Nies Annemien , Ryan Jillian C. 
Published: November 2021

Abstract
Background
Co-design has the potential to create interventions that lead to sustainable health behaviour change. Evidence suggests application of co-design in various health domains has been growing; however, few public-facing digital interventions have been co-designed to specifically address the needs of adults at risk of Type 2 diabetes (T2D). This study aims to: (1) co-design, with key stakeholders, a digital dietary intervention to promote health behaviour change among adults at risk of T2D, and (2) evaluate the co-design process involved in developing the intervention prototype.

Methods
The co-design study was based on a partnership between nutrition researchers and designers experienced in co-design for health. Potential end-users (patients and health professionals) were recruited from an earlier stage of the study. Three online workshops were conducted to develop and review prototypes of an app for people at risk of T2D. Themes were inductively defined and aligned with persuasive design (PD) principles used to inform ideal app features and characteristics.

Results
Participants were predominantly female (range 58–100%), aged 38 to 63 years (median age = 59 years), consisting of a total of 20 end-users and four experts. Participants expressed the need for information from credible sources and to provide effective strategies to overcome social and environmental influences on eating behaviours. Preferred app features included tailoring to the individual’s unique characteristics, ability to track and monitor dietary behaviour, and tools to facilitate controlled social connectivity. Relevant persuasive design principles included social support, reduction (reducing effort needed to reach target behaviour), tunnelling (guiding users through a process that leads to target behaviour), praise, rewards, and self-monitoring. The most preferred prototype was the Choices concept, which focusses on the users’ journey of health behaviour change and recognises progress, successes, and failures in a supportive and encouraging manner. The workshops were rated successful, and feedback was positive.

Conclusions
The study’s co-design methods were successful in developing a functionally appealing and relevant digital health promotion intervention. Continuous engagement with stakeholders such as designers and end-users is needed to further develop a working prototype for testing.
Impacts of chronic disease prevention programs implemented by private health insurers: a systematic review
Authors: Wanni Arachchige Dona Sithara , Angeles Mary Rose , Hall Natasha , Watts Jennifer J. , Peeters Anna , Hensher Martin 
Published: November 2021

Abstract
Background
Chronic diseases contribute to a significant proportion (71%) of all deaths each year worldwide. Governments and other stakeholders worldwide have taken various actions to tackle the key risk factors contributing to the prevalence and impact of chronic diseases. Private health insurers (PHI) are one key stakeholders, particularly in Australian health system, and their engagement in chronic disease prevention is growing. Therefore, we investigated the impacts of chronic disease prevention interventions implemented by PHI both in Australia and internationally.

Method
We searched multiple databases (Business Source Complete, CINAHL, Global Health, Health Business Elite, Medline, PsycINFO, and Scopus) and grey literature for studies/reports published in English until September 2020 using search terms on the impacts of chronic disease prevention interventions delivered by PHIs. Two reviewers assessed the risk of bias using a quality assessment tool developed by Effective Public Healthcare Panacea Project. After data extraction, the literature was synthesised thematically based on the types of the interventions reported across studies. The study protocol was registered in PROSPERO, CRD42020145644.

Results
Of 7789 records, 29 studies were eligible for inclusion. There were predominantly four types of interventions implemented by PHIs: Financial incentives, health coaching, wellness programs, and group medical appointments. Outcome measures across studies were varied, making it challenging to compare the difference between the effectiveness of different intervention types. Most studies reported that the impacts of interventions, such as increase in healthy eating, physical activity, and lower hospital admissions, last for a shorter term if the length of the intervention is shorter.

Interpretation
Although it is challenging to conclude which intervention type was the most effective, it appeared that, regardless of the intervention types, PHI interventions of longer duration (at least 2 years) were more beneficial and outcomes were more sustained than those PHI interventions that lasted for a shorter period.

Funding
Primary source of funding was Geelong Medical and Hospital Benefits Association (GMHBA), an Australian private health insurer.
Accelerating Sustainable Development Goals for South African adolescents from high HIV prevalence areas: a longitudinal path analysis
Authors: Meinck Franziska , Orkin Mark , Cluver Lucie 
Published: November 2021

Abstract
Background
Adolescents experience a multitude of vulnerabilities which need to be addressed in order to achieve the Sustainable Development Goals (SDGs). In sub-Saharan Africa, adolescents experience high burden of HIV, violence exposure, poverty, and poor mental and physical health. This study aimed to identify interventions and circumstances associated with three or more targets (“accelerators”) within multiple SDGs relating to HIV-affected adolescents and examine cumulative effects on outcomes.

Methods
Prospective longitudinal data from 3401 adolescents from randomly selected census enumeration areas in two provinces with > 30% HIV prevalence carried out in 2010/11 and 2011/12 were used to examine six hypothesized accelerators (positive parenting, parental monitoring, free schooling, teacher support, food sufficiency and HIV-negative/asymptomatic caregiver) targeting twelve outcomes across four SDGs, using a multivariate (multiple outcome) path model with correlated outcomes controlling for outcome at baseline and socio-demographics. The study corrected for multiple-hypothesis testing and tested measurement invariance across sex. Percentage predicted probabilities of occurrence of the outcome in the presence of the significant accelerators were also calculated.

Results
Sample mean age was 13.7 years at baseline, 56.6% were female. Positive parenting, parental monitoring, food sufficiency and AIDS-free caregiver were variously associated with reductions on ten outcomes. The model was gender invariant. AIDS-free caregiver was associated with the largest reductions. Combinations of accelerators resulted in a percentage reduction of risk of up to 40%.

Conclusion
Positive parenting, parental monitoring, food sufficiency and AIDS-free caregivers by themselves and in combination improve adolescent outcomes across ten SDG targets. These could translate to the corresponding real-world interventions parenting programmes, cash transfers and universal access to antiretroviral treatment, which when provided together, may help governments in sub-Saharan Africa more economically to reach their SDG targets.
Investigation on factors associated with ovarian cancer: an umbrella review of systematic review and meta-analyses
Authors: Tanha Kiarash , Mottaghi Azadeh , Nojomi Marzieh , Moradi Marzieh , Rajabzadeh Rezvan , Lotfi Samaneh , Janani Leila 
Published: November 2021

AbstractFollowing cervical and uterine cancer, ovarian cancer (OC) has the third rank in gynecologic cancers. It often remains non-diagnosed until it spreads throughout the pelvis and abdomen. Identification of the most effective risk factors can help take prevention measures concerning OC. Therefore, the presented review aims to summarize the available studies on OC risk factors. A comprehensive systematic literature search was performed to identify all published systematic reviews and meta-analysis on associated factors with ovarian cancer. Web of Science, Cochrane Library databases, and Google Scholar were searched up to 17th January 2020. This study was performed according to Smith et al. methodology for conducting a systematic review of systematic reviews. Twenty-eight thousand sixty-two papers were initially retrieved from the electronic databases, among which 20,104 studies were screened. Two hundred seventy-seven articles met our inclusion criteria, 226 of which included in the meta-analysis. Most commonly reported genetic factors were MTHFR C677T (OR=1.077; 95 % CI (1.032, 1.124); P-value<0.001), BSML rs1544410 (OR=1.078; 95 %CI (1.024, 1.153); P-value=0.004), and Fokl rs2228570 (OR=1.123; 95 % CI (1.089, 1.157); P-value<0.001), which were significantly associated with increasing risk of ovarian cancer. Among the other factors, coffee intake (OR=1.106; 95 % CI (1.009, 1.211); P-value=0.030), hormone therapy (RR=1.057; 95 % CI (1.030, 1.400); P-value<0.001), hysterectomy (OR=0.863; 95 % CI (0.745, 0.999); P-value=0.049), and breast feeding (OR=0.719, 95 % CI (0.679, 0.762) and P-value<0.001) were mostly reported in studies. Among nutritional factors, coffee, egg, and fat intake significantly increase the risk of ovarian cancer. Estrogen, estrogen-progesterone, and overall hormone therapies also are related to the higher incidence of ovarian cancer. Some diseases, such as diabetes, endometriosis, and polycystic ovarian syndrome, as well as several genetic polymorphisms, cause a significant increase in ovarian cancer occurrence. Moreover, other factors, for instance, obesity, overweight, smoking, and perineal talc use, significantly increase the risk of ovarian cancer.
ATRX regulates glial identity and the tumor microenvironment in IDH-mutant glioma
Authors: Babikir Husam , Wang Lin , Shamardani Karin , Catalan Francisca , Sudhir Sweta , Aghi Manish K. , Raleigh David R. , Phillips Joanna J. , Diaz Aaron A. 
Published: November 2021

Abstract
Background
Recent single-cell transcriptomic studies report that IDH-mutant gliomas share a common hierarchy of cellular phenotypes, independent of genetic subtype. However, the genetic differences between IDH-mutant glioma subtypes are prognostic, predictive of response to chemotherapy, and correlate with distinct tumor microenvironments.

Results
To reconcile these findings, we profile 22 human IDH-mutant gliomas using scATAC-seq and scRNA-seq. We determine the cell-type-specific differences in transcription factor expression and associated regulatory grammars between IDH-mutant glioma subtypes. We find that while IDH-mutant gliomas do share a common distribution of cell types, there are significant differences in the expression and targeting of transcription factors that regulate glial identity and cytokine elaboration. We knock out the chromatin remodeler ATRX, which suffers loss-of-function alterations in most IDH-mutant astrocytomas, in an IDH-mutant immunocompetent intracranial murine model. We find that both human ATRX-mutant gliomas and murine ATRX-knockout gliomas are more heavily infiltrated by immunosuppressive monocytic-lineage cells derived from circulation than ATRX-intact gliomas, in an IDH-mutant background. ATRX knockout in murine glioma recapitulates gene expression and open chromatin signatures that are specific to human ATRX-mutant astrocytomas, including drivers of astrocytic lineage and immune-cell chemotaxis. Through single-cell cleavage under targets and tagmentation assays and meta-analysis of public data, we show that ATRX loss leads to a global depletion in CCCTC-binding factor association with DNA, gene dysregulation along associated chromatin loops, and protection from therapy-induced senescence.

Conclusions
These studies explain how IDH-mutant gliomas from different subtypes maintain distinct phenotypes and tumor microenvironments despite a common lineage hierarchy.