bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statistical and Bioinformatic Analysis of Hemimethylation Patterns in Non-Small Cell Lung Cancer
Authors: Sun Shuying , Zane Austin , Fulton Carolyn , Philipoom Jasmine 
Published: October 2020

Abstract
Background: DNA methylation is an epigenetic event involving the addition of a methyl-group to a cytosine-guanine base pair (i.e., CpG site). It is associated with different cancers. Our research focuses on studying non-small cell lung cancer hemimethylation, which refers to methylation occurring on only one of the two DNA strands. Many studies often assume that methylation occurs on both DNA strands at a CpG site. However, recent publications show the existence of hemimethylation and its significant impact. Therefore, it is important to identify cancer hemimethylation patterns. Methods: In this paper, we use the Wilcoxon signed rank test to identify hemimethylated CpG sites based on publicly available non-small cell lung cancer methylation sequencing data. We then identify two types of hemimethylated CpG clusters, regular and polarity clusters, and genes with large numbers of hemimethylated sites. Highly hemimethylated genes are then studied for their biological interactions using available bioinformatics tools. Results: In this paper, we have conducted the first-ever investigation of hemimethylation in lung cancer. Our results show that hemimethylation does exist in lung cells either as singletons or clusters. Most clusters contain only two or three CpG sites. Polarity clusters are much shorter than regular clusters and appear less frequently. The majority of clusters found in tumor samples have no overlap with clusters found in normal samples, and vice versa. Several genes that are known to be associated with cancer are hemimethylated differently between the cancerous and normal samples. Furthermore, highly hemimethylated genes exhibit many different interactions with other genes that may be associated with cancer. Hemimethylation has diverse patterns and frequencies that are comparable between normal and tumorous cells. Therefore, hemimethylation may be related to both normal and tumor cell development. Conclusions: Our research has identified CpG clusters and genes that are hemimethylated in normal and lung tumor samples. Due to the potential impact of hemimethylation on gene expression and cell function, these clusters and genes may be important to advance our understanding of the development and progression of non-small cell lung cancer.
Communication patterns in the doctor–patient relationship: evaluating determinants associated with low paternalism in Mexico.
Authors: Lazcano-Ponce Eduardo , Angeles-Llerenas Angelica , Rodríguez-Valentín Rocío , Salvador-Carulla Luis , Domínguez-Esponda Rosalinda , Astudillo-García Claudia Iveth , de León Eduardo Madrigal , Katz Gregorio 
Published: October 2020

Abstract
Background: Paternalism/overprotection limits communication between healthcare professionals and patients and does not promote shared therapeutic decision-making. In the global north, communication patterns have been regulated to promote autonomy, whereas in the global south, they reflect the physician’s personal choices. The goal of this work was contribute to knowledge of the communication patterns used in clinical practice in Mexico and to identify the determinants that favour a doctor-patient relationship characterized by low paternalism/autonomy.Methods: A self-report study of communication patterns within a sample of 761 mental healthcare professionals in Central and Western Mexico was conducted. Multiple ordinal logistic regression models were performed to analyse paternalism and associated factors. Results: A high prevalence (68.7% [95% CI 60.0-70.5]) of paternalism was observed among mental healthcare professionals in Mexico. The main determinants of low paternalism/autonomy were medical specialty (OR 1.67 [95% CI 1.16-2.40]) and gender, with female physicians more likely to explicitly share diagnoses and therapeutic strategies with patients and their families (OR 1.57 [95% CI 1.11-2.22]). A pattern of highly explicit communication was strongly associated with low paternalism/autonomy (OR 12.13 [95% CI 7.71-19.05]). Finally, a modifying effect of age strata on the association between communication pattern or specialty and low paternalism/autonomy was observed.Conclusions: Among mental healthcare professionals in Mexico, an elevated paternalism prevailed. Gender, specialty, and a pattern of open communication were closely associated with low paternalism/autonomy. Strengthening the competencies of health professionals and promoting explicit communication could contribute to the transition towards more autonomist communication in clinical practice in Mexico. The ethical implications will need to be resolved in the near future.
Gene expression-based immune infiltration analyses of renal cancer and their associations with survival outcome
Authors: Chen Lei , Yin Liang , Qi Zilong , Li Jinmin , Wang Xinning , Ma Kun , Liu Xiangyang 
Published: October 2020

Abstract
Background: Renal cancer is a common malignant tumor with an increasing incidence rate.Methods: In this study, based on the gene expression profiles, we analyzed the compositions of tumor-infiltrating immune cells (TIICs) in renal cancer and paracancerous samples using CIBERSORT. The proportions of 22 TIICs subsets in 122 paired renal carcinoma and paracancerous samples, and 224 Wilms tumor (WT) samples varied between intragroup and intergroup. Results: After analyzed the difference of TIICs composition between renal cancer and paired paracancerous samples, we found that M0 macrophages and CD8 T cells were significantly elevated, while naive B cells were significantly decreased in renal cancer samples compared with paracancerous samples. Survival analysis showed that high overall TIICs proportion, the low proportion of resting mast cells and the high proportion of activated memory CD4 T cells were associated with poor prognosis of renal cancer patients. In addition, 3 clusters were identified by hierarchical clustering analysis, and they presented a distinct prognosis. Cluster 1 had superior survival outcomes, while cluster 2 had an inferior survival outcome.Conclusions: Our study indicated that overall TIICs proportion, certain TIICs subset proportion, including resting mast cells and activated memory CD4 T cells, and distinct cluster patterns were associated with the prognosis of renal cancer, which was significant for the clinical surveillance and treatment of renal cancer.
Functional polymorphisms and transcriptional analysis in the 5' region of the human serotonin receptor 1B gene (HTR1B) and their associations with psychiatric disorders
Authors: Xia Xi , Ding Mei , Xuan Jin-feng , Xing Jia-xin , Yao Jun , Wu Xue , Wang Bao-jie 
Published: October 2020

Abstract
Background The 5-hydroxytryptamine 1B receptor (5-HT1B) plays an essential role in the serotonin (5-HT) system and is widely involved in a variety of brain activities. HTR1B is the gene encoding 5-HT1B. Genome-wide association studies have shown that HTR1B polymorphisms are closely related to multiple mental and behavioral disorders; however, the functional mechanisms underlying these associations are unknown. This study investigated the effect of several HTR1B haplotypes on regulation of gene expression in vitro and the functional sequences in the 5' regulatory region of HTR1B to determine their potential association with mental and behavioral disorders. Methods Six haplotypes consisting of rs4140535, rs1778258, rs17273700, rs1228814, rs11568817, and rs130058 and several truncated fragments of the 5' regulatory region of HTR1B were transfected into SK-N-SH and HEK-293 cells. The relative fluorescence intensities of the different haplotypes and truncated fragments were detected using a dual-luciferase reporter assay system. Results Compared to the major haplotype T-G-T-C-T-A, the relative fluorescence intensities of haplotypes C-A-T-C-T-A, C-G-T-C-T-A, C-G-C-A-G-T, and C-G-T-A-T-A were significantly lower, and that of haplotype C-G-C-A-G-A was significantly higher. Furthermore, the effects of the rs4140535T allele, the rs17273700C-rs11568817G linkage combination, and the rs1228814A allele made their relative fluorescence intensities significantly higher than their counterparts at each locus. Conversely, the rs1778258A and rs130058T alleles decreased the relative fluorescence intensities. In addition, we found that regions from -1587 to -1371 bp (TSS, +1), -1149 to -894 bp, -39 to +130 bp, +130 to +341 bp, and +341 to +505 bp upregulated gene expression. In contrast, regions -603 to -316 bp and +130 to +341 bp downregulated gene expression. Region +341 to +505 bp played a decisive role in gene transcription. Conclusions HTR1B 5' regulatory region polymorphisms have regulatory effects on gene expression and potential correlate with several pathology and physiology conditions. This study suggests that a crucial sequence for transcription is located in region +341~+505 bp. Regions -1587 to -1371 bp, -1149 to -894 bp, -603 to -316 bp, -39 to +130 bp, and +130 to +341 bp contain functional sequences that can promote or suppress the HTR1B gene expression.
The awareness, visibility and support for young carers across Europe: a Delphi study
Authors: Nap Henk Herman , Hoefman Renske , de Jong Nynke , Lovink Lieke , Glimmerveen Ludo , Lewis Feylyn , Santini Sara , D’Amen Barbara , Socci Marco , Boccaletti Licia , Casu Giulia , Manattini Alessandra , Brolin Rosita , Sirk Karina , Hlebec Valentina , Rakar Tatjana , Hudobivnik Tjasa , Leu Agnes , Berger Fabian , Magnusson Lennart , Hanson Elizabeth 
Published: October 2020

Abstract
Background Across Europe, young carers (YCs) and their need for support receive limited attention in the media, policy and empirical research, even though, similar to adult carers, they also provide care to ill family members. The Delphi study, a qualitative research methodology, which provides the focus for this article, had the overall aim of exploring existing successful strategies to support YCs. Compared to YCs, even less is known about adolescent young carers (AYCs), a group that is in a critical life transition phase. The study forms part of an EU Horizon 2020 funded research project on AYCs aged 15-17 years old. Methods A two-round Delphi study was conducted with 66 experts on YCs from 10 European countries. Topics included: (i) visibility and awareness-raising of YCs at local, regional, and national levels, (ii) current interventions to support YCs, and (iii) future strategies to support YCs. Results Experts reported a lack of visibility and awareness about YCs in general, and AYCs in particular. Although awareness is slowly increasing in most countries, with the UK ranked highest, experts acknowledged that it remains challenging to identify YCs in many countries. Furthermore, the level and type of support available for YCs differs, with most countries mainly offering support on a local level. Diverse views were expressed regarding future strategies to support YCs. Experts highlighted the importance of specific legislation to formalise the rights of YCs, and the issue of whether young people should be safeguarded from caregiving or if this should be considered part of regular family life. They also emphasised the relevance of available integrated support services for YCs, including schools, family, health and social care. Conclusions In most European countries, there is a lack of awareness and visibility on YCs. Identification of YCs is a crucial first step and there is need for a common definition of YCs, together with greater opportunities for young adults to identify themselves as YCs.
Managerial features and outcome in neonatal intensive care units: results from a cluster analysis
Authors: Fanelli Simone , Bellù Roberto , Zangrandi Antonello , Gagliardi Luigi , Zanini Rinaldo 
Published: October 2020

Abstract
Background: Healthcare organisations differ in performance even if they are located in the same country or region. Suitable managerial practices and organisational processes can lead to better health outcomes. As a result, hospitals are constantly looking for managerial arrangements that can improve outcomes and keep costs down. This study aims to identify different managerial models in neonatal intensive care units (NICUs) and their impact on a large number of outcomes. Methods: The research was conducted in Italy, within the SONAR project. SONAR’s aim was to identify the characteristics of NICUs, monitor outcomes and promote best practices. This study includes 51 of the 63 NICUs that took part in the SONAR project. Questionnaires on the activities and managerial features were administered to doctors and nurses working in NICUs. A total of 643 questionnaires were analysed from doctors and a total of 1,601 from nurses. A cluster analysis was performed to identify managerial models of NICUs.Results: Three managerial models emerged from cluster analysis: traditional, collaborative and individualistic. In the “traditional” model the doctor is above the nurse in the hierarchy, and the nurse therefore has exclusively operational autonomy. The “collaborative” model has as key elements professional specialisation and functional coordination. The “individualistic” model considers only individual professional skills and does not concern the organisational conditions necessary to generate organisational effectiveness.The results also showed that there is an association between managerial model and neonatal outcomes. The collaborative model shows best results in almost all outcomes considered, and the traditional model has the worst. The individualistic model is in the middle, although its values are very close to those of traditional model.Conclusions: Health management needs to assess NICU strategically in order to develop models to improve outcomes. This study provides insights for management useful for designing managerial characteristics of NICUs in order to achieve better results. NICUs characterised by a collaborative model in fact show better neonatal outcomes.
Clinicians’ Experience of Providing Care: A Rapid Review
Authors: Iqbal Maha Pervaz , Manias Elizabeth , Mimmo Laurel , Mears Stephen , Jack Briony , Hay Liz , Harrison Reema 
Published: October 2020

Abstract
Background Health care services internationally are refocussing care delivery towards patient centred, integrated care that utilises effective, efficient and innovative models of care to optimise patient outcomes and system sustainability. Whilst significant efforts have been made to examine and enhance patient experience, to date little has progressed in relation to provider experience. This review aims to explore this knowledge gap by capturing evidence of clinician experience, and how this experience is defined and measured in the context of health system change and innovation.Methods A rapid review of published and grey literature review was conducted utilising a rapid evidence assessment methodology. 79 studies retrieved from the literature were included in the review. 14 articles were identified from the grey literature search and one article obtained via hand searching. In total, 94 articles were included in the review. This study was commissioned by and co-designed with the New South Wales, Ministry of Health.Results Clinician experience of delivering health care is inconsistently defined in the literature, with identified articles lacking clarity regarding distinctions between experience, engagement and work-related outcomes such as job satisfaction. Clinician experience was commonly explored using qualitative research that focused on experiences of discrete health care activities or events in which a change was occurring. Such research enabled exploration of complex experiences. In these contexts, clinician experience was captured in terms of self-reported information that clinicians provided about the health care activity or event, their perceptions of its value, the lived impacts they experienced, and the specific behaviours they displayed in relation to the activity or event. Moreover, clinician’s experience has been identified to have a paucity of measurement tools. Conclusion Literature to date has not examined clinician experience in a holistic sense. In order to achieve the goals identified in relation to value-based care, further work is needed to conceptualise clinician experience and understand the nature of measurement tools required to assess this. In health system application, a broader ‘clinician pulse’ style assessment may be valuable to understand the experience of clinical work on a continuum rather than in the context of episodes of change/care.
Prevalence of musculoskeletal conditions and related disabilities in Bangladeshi adults: a cross-sectional national survey
Authors: Zahid-Al-Quadir Ahmad , Zaman Mohammad Mostafa , Ahmed Shamim , Bhuiyan Mahfuzur Rahman , Rahman Md Mujibur , Patwary Ismail , Das Bidhu Bhushan , Hossain Shaikh Amir , Paul Sujat , Shahin Abu , Rahman Mashiur , Haq Syed Atiqul 
Published: October 2020

Abstract
Background: Nationally representative data on burden of musculoskeletal conditions (MSK) in Bangladesh are not available. The objective of this study was to determine the prevalence of MSK conditions and related disabilities in the adult population of Bangladesh.Methods: A total of 2000 individuals aged 18 years or older were targeted from 20 primary sampling units (urban and rural) of all former seven divisions of Bangladesh in 2015. Structured interviews were done using the modified Community Oriented Program for Control of Rheumatic Disorders questionnaire to detect positive respondents. Standard criteria were used for diagnosing MSK conditions by rheumatology residents. In case of uncertainty, opinion was taken from senior rheumatologists. A Bangla version of the Health Assessment Questionnaire was used to determine disability.Results: A total of 1843 (92.1%) participated. Among them, 892 men and 951 women participated from rural (n=716) and urban (n=1127) areas. Their mean age was 40.5 (standard deviation 14.7) years. Almost a third did not have any formal schooling. Overall, 30.4% (95% confidence interval, 28.3-32.5) had MSK conditions. Low back pain (18.6%, 16.9-20.5), knee osteoarthritis (7.3%, 6.1-8.5) and soft tissue rheumatism 3.8% (2.9-4.7) were the three top-ranking MSK conditions. Rheumatoid arthritis (1.6%, 1.0-2.1), spondyloarthritis (1.2%, 7-1.8) and adhesive capsulitis (1.4%, 0.9-1.9) were relatively uncommon. Among those who had MSK conditions, 24.8% (21.3-28.6) had some degree of disability. Of them, 24.4% (21.0-28.1) had history of work loss during last 12 months. Conclusions: The high burden of MSK conditions and related disabilities in Bangladesh warrants greater attention of the health system. Further studies are needed to estimate the impact of this group of conditions particularly addressing related disabilities and loss of work.
Differential transcriptomics in sarcoidosis lung and lymph node granulomas with comparisons to pathogen-specific granulomas
Authors: Casanova Nancy G. , Gonzalez-Garay Manuel L , Sun Belinda , Bime Christian , Knox Kenneth S. , Crouser Elliot , Sun Xiaoguang , Sammani Nora , Gregory Taylor , Natt Bhupinder , Chaudhary Sachin , Lussier Yves , Garcia Joe G. N. 
Published: October 2020

Abstract
Rationale: Despite the availability of multi-“omics” strategies, insights into the etiology and pathogenesis of sarcoidosis have been elusive. This is partly due to the lack of reliable preclinical models and a paucity of validated biomarkers. As granulomas are a key feature of sarcoidosis, we speculate that direct genomic interrogation of sarcoid tissues, may lead to identification of dysregulated gene pathways or biomarker signatures.Objective: To facilitate the development sarcoidosis genomic biomarkers by gene expression profiling of sarcoidosis granulomas in lung and lymph node tissues (most commonly affected organs) and comparison to infectious granulomas (coccidiodomycosis and tuberculosis).Methods: Transcriptomic profiles of immune-related gene from micro-dissected sarcoidosis granulomas within lung and mediastinal lymph node tissues and compared to infectious granulomas from paraffin-embedded blocks. Differentially-expressed genes (DEGs) were profiled, compared among the three granulomatous diseases and analyzed for functional enrichment pathways.Results: Despite histologic similarities, DEGs and pathway enrichment markedly differed in sarcoidosis granulomas from lymph nodes and lung. Lymph nodes showed a clear immunological response, whereas a structural regenerative response was observed in lung. Sarcoidosis granuloma gene expression data corroborated previously reported genomic biomarkers (STAB1, HBEGF, and NOTCH4), excluded others and identified new genomic markers present in lung and lymph nodes, ADAMTS1, NPR1 and CXCL2. Comparisons between sarcoidosis and pathogen granulomas identified pathway divergences and commonalities at gene expression level.Conclusion: These findings suggest the importance of tissue and disease-specificity evaluation when exploring sarcoidosis genomic markers. This relevant translational information in sarcoidosis and other two histopathological similar infections provides meaningful specific genomic-derived biomarkers for sarcoidosis diagnosis and prognosis.
Long non-coding RNA SNHG15 in various cancers: a meta and bioinformatic analysis
Authors: Chen Caizhi , Feng Yeqian , Wang Jingjing , Liang Ye , Zou Wen 
Published: October 2020

Abstract
Background: The snoRNA host gene SNHG15 produces a long non‐coding RNA (lncRNA) with a short half-life and has been reported to be dysregulated in multiple cancers and has recently been found to be correlated with tumour progression. Therefore, this meta-analysis was performed to evaluate the generalised prognostic role of small nucleolar RNA host gene 15 (SNHG15) in malignancies, based on variable data from different studies.Methods: Four public databases were used to identify eligible studies. The association between prognostic indicators and clinical features was extracted and pooled to estimate the hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs). Publication bias was measured using Begg’s test and Egger’s test, and the stability of pooled results were measured using sensitivity analysis. Additionally, an online database based on The Cancer Genome Atlas (TCGA) was screened to further validate our results.Results: In total, 11 studies including 1,087 patients were ultimately enrolled in our meta-analysis. We found that SNHG15 overexpression was associated with worse overall survival (OS) and disease-free survival (DFS), and this was validated in the Gene Expression Profiling Interactive Analysis (GEPIA) cohort. Moreover, increased SNHG15 expression suggested advanced TNM stage and LNM, but was not associated with age, gender, or tumour size. No publication bias or instability of the results was observed. SNHG15 was significantly upregulated in seven cancers and elevated expression of SNHG15 indicated shorter OS and DFS in five malignancies based on the validation using the GEPIA cohort.Conclusions: Upregulation of lncRNA SNHG15 was notably associated with worse prognosis and clinical features, suggesting that SNHG15 might serve as a novel prognostic factor in various cancers.