bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impacts of the SOAT1 genetic variants and protein expression on HBV-related hepatocellular carcinoma
Authors: Chen Yulong , Yang Xunjun , Chen Yao , Chen Guorong , Winkler Cheryl A. , An Ping , Lyu Jianxin 
Published: May 2021

Abstract
Background
Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains a major public health problem and its pathogenesis remains unresolved. A recent proteomics study discovered a lipid enzyme Sterol O-acyltransferase (SOAT1) involvement in the progression of HCC. We aimed to explore the association between SOAT1 genetic variation and HCC.

Methods
We genotyped three exonic SOAT1 variants (rs10753191, V323V; rs3753526, L475L; rs13306731, Q526R) tagging most variations in the gene, in 221 HCC patients and 229 healthy individuals, to assess the impact of SOAT1 gene variation on risk of HCC occurrence. We further conducted immunohistochemistry to compare SOAT1 protein expression levels in 42 paired tumor and adjacent non-tumor tissues.

Results
We found that rs10753191 (Odds ratio (OR) = 0.58, P = 0.04) and a haplotype TGA (OR = 0.40, P = 0.01) were associated with reduced HCC risk after adjusting for lipid levels. In the immunohistochemistry experiment, we found that the protein expression of SOAT1 was significantly increased in the tumor compared with adjacent tissue (P < 0.001).

Conclusion
This study revealed for the first time SOAT1 genetic variation that associates with host susceptibility to HCC occurrence. Our results suggest a role of SOAT1 in the HCC development, which warrants further elucidation.
Identification of significant genes as prognostic markers and potential tumor suppressors in lung adenocarcinoma via bioinformatical analysis
Authors: Lu Mingze , Fan Xiaowen , Liao Weilin , Li Yijiao , Ma Lijie , Yuan Mu , Gu Rui , Wei Zhengdao , Wang Chao , Zhang Hua 
Published: May 2021

Abstract
Background
Lung adenocarcinoma (LAC) is the predominant histologic subtype of lung cancer and has a complicated pathogenesis with high mortality. The purpose of this study was to identify differentially expressed genes (DEGs) with prognostic value and determine their underlying mechanisms.

Methods
Gene expression data of GSE27262 and GSE118370 were acquired from the Gene Expression Omnibus database, enrolling 31 LAC and 31 normal tissues. Common DEGs between LAC and normal tissues were identified using the GEO2R tool and Venn diagram software. Next, the Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used to analyze the Gene Ontology and Kyoto Encyclopedia of Gene and Genome (KEGG) pathways. Then, protein-protein interaction (PPI) network of DEGs was visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes and central genes were identified via Molecular Complex Detection. Furthermore, the expression and prognostic information of central genes were validated via Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan-Meier analysis, respectively. Finally, DAVID, real-time PCR and immunohistochemistry were applied to re-analyze the identified genes, which were also further validated in two additional datasets from ArrayExpress database.

Results
First, 189 common DEGs were identified among the two datasets, including 162 downregulated and 27 upregulated genes. Next, Gene Ontology and KEGG pathway analysis of the DEGs were conducted through DAVID. Then, PPI network of DEGs was constructed and 17 downregulated central genes were identified. Furthermore, the 17 downregulated central genes were validated via GEPIA and datasets from ArrayExpress, and 12 of them showed a significantly better prognosis. Finally, six genes were identified significantly enriched in neuroactive ligand-receptor interactions (EDNRB, RXFP1, P2RY1, CALCRL) and Rap1 signaling pathway (TEK, P2RY1, ANGPT1) via DAVID, which were further validated to be weakly expressed in LAC tissues via RNA quantification and immunohistochemistry analysis.

Conclusions
The low expression pattern and relation to prognosis indicated that the six genes were potential tumor suppressor genes in LAC. In conclusion, we identified six significantly downregulated DEGs as prognostic markers and potential tumor suppressor genes in LAC based on integrated bioinformatics methods, which could act as potential molecular markers and therapeutic targets for LAC patients.
Safety and efficacy profile of mogamulizumab (Poteligeo) in the treatment of cancers: an update evidence from 14 studies
Authors: Zhang Ting , Sun Jing , Li Jinying , Zhao Yunuo , Zhang Tao , Yang Ruoning , Ma Xuelei 
Published: May 2021

Abstract
Background
CC chemokine receptor 4 (CCR4), the receptor for CCL22 and CCL17, is expressed on the surface of effector Tregs that have the highest suppressive effects on antitumor immune response. CCR4 is also widely expressed on the surface of tumor cells from patients with adult T-cell leukemia/lymphoma (ATL), peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL). Mogamulizumab is a humanized, IgG1 kappa monoclonal antibody that is directed against CCR4. By reducing the number of CCR4-positive Tregs and tumor cells, the mogamulizumab can reduce tumor burden and boost antitumor immunity to achieve antitumor effects.

Methods
We examined the PubMed and ClinicalTrials.gov until 1 February 2020. Considering variability in different studies, we selected the adverse events (AEs), overall survival (OS), progression-free survival (PFS), objective responses rate (ORR) and Hazard Ratio (HR) for PFS to evaluate the safety and efficacy profile of mogamulizumab.

Results
When patients were treated with mogamulizumab monotherapy, the most common all-grade AEs were lymphopenia, infusion reaction, fever, rash and chills while the most common grade ≥ 3 AEs were lymphopenia, neutropenia and rash. When patients were treated with combined therapy of mogamulizumab and other drugs, the most common all-grade AEs were neutropenia, anaemia, lymphopenia and gastrointestinal disorder, while the most common grade ≥ 3 AEs was lymphopenia. For patients treated with mogamulizumab monotherapy, the pooled ORR and mean PFS were 0.430 (95% CI: 0.393–0.469) and 1.060 months (95% CI: 1.043–1.077), respectively. For patients treated with combined therapy of mogamulizumab and other drugs, the pooled ORR was 0.203 (95% CI: 0.022–0.746) while the pooled PFS and OS were 2.093 months (95% CI: 1.602–2.584) and 6.591 months (95% CI: 6.014–7.167), respectively.

Conclusions
Based on present evidence, we believed that mogamulizumab had clinically meaningful antitumor activity with acceptable toxicity which is a novel therapy in treating patients with cancers.
Body-mass index, blood pressure, diabetes and cardiovascular mortality in Cuba: prospective study of 146,556 participants
Authors: Armas Rojas Nurys B , Lacey Ben , Soni Monica , Charles Shaquille , Carter Jennifer , Varona-Pérez Patricia , Burrett Julie Ann , Martínez Marcy Calderón , Lorenzo-Vázquez Elba , Constantén Sonia Bess , Taylor Hannah , Sherliker Paul , Rigau José Manuel Morales , Ross Stephanie , Massa M. Sofia , López Osvaldo Jesús Hernández , Islam Nazrul , Morales Miguel Ángel Martínez , Alomá Ismell Alonso , Estupiñan Fernando Achiong , González Mayda Díaz , Muñoz Noel Rosquete , Asencio Marelis Cendra , Díaz-Diaz Oscar , Iglesias-Marichal Ileydis , Emberson Jonathan , Peto Richard , Lewington Sarah 
Published: May 2021

Abstract
Background
Cardiovascular disease accounts for about one-third of all premature deaths (ie, age < 70) in Cuba. Yet, the relevance of major risk factors, including systolic blood pressure (SBP), diabetes, and body-mass index (BMI), to cardiovascular mortality in this population remains unclear.

Methods
In 1996–2002, 146,556 adults were recruited from the general population in five areas of Cuba. Participants were interviewed, measured (height, weight and blood pressure) and followed up by electronic linkage to national death registries until Jan 1, 2017; in 2006–08, 24,345 participants were resurveyed. After excluding all with missing data, cardiovascular disease at recruitment, and those who died in the first 5 years, Cox regression (adjusted for age, sex, education, smoking, alcohol and, where appropriate, BMI) was used to relate cardiovascular mortality rate ratios (RRs) at ages 35–79 years to SBP, diabetes and BMI; RR were corrected for regression dilution to give associations with long-term average (ie, ‘usual’) levels of SBP and BMI.

Results
After exclusions, there were 125,939 participants (mean age 53 [SD12]; 55% women). Mean SBP was 124 mmHg (SD15), 5% had diabetes, and mean BMI was 24.2 kg/m2 (SD3.6); mean SBP and diabetes prevalence at recruitment were both strongly related to BMI. During follow-up, there were 4112 cardiovascular deaths (2032 ischaemic heart disease, 832 stroke, and 1248 other). Cardiovascular mortality was positively associated with SBP (>=120 mmHg), diabetes, and BMI (>=22.5 kg/m2): 20 mmHg higher usual SBP about doubled cardiovascular mortality (RR 2.02, 95%CI 1.88–2.18]), as did diabetes (2.15, 1.95–2.37), and 10 kg/m2 higher usual BMI (1.92, 1.64–2.25). RR were similar in men and in women. The association with BMI and cardiovascular mortality was almost completely attenuated following adjustment for the mediating effect of SBP. Elevated SBP (>=120 mmHg), diabetes and raised BMI (>=22.5 kg/m2) accounted for 27%, 14%, and 16% of cardiovascular deaths, respectively.

Conclusions
This large prospective study provides direct evidence for the effects of these major risk factors on cardiovascular mortality in Cuba. Despite comparatively low levels of these risk factors by international standards, the strength of their association with cardiovascular death means they nevertheless exert a substantial impact on premature mortality in Cuba.
Application of the health action process approach model for reducing excessive internet use behaviors among rural adolescents in China: a school-based intervention pilot study
Authors: Tang Chengmeng , Raat Hein , Yan Mingxia , Zhang Qiang , Li Kehan , Jiang Min , Tang Wanjie , Chen Jiayi , Zhao Ying , Liu Qiaolan 
Published: May 2021

Abstract
Objective
There are few studies regarding Internet use behaviors of Chinese rural adolescents based on behavioral theory. The aim of this study is to examine the applicability and effectiveness of the health action process approach model (HAPA) in the intervention of excessive Internet use behaviors among rural adolescents in China.

Methods
Three hundred twenty-seven participants who met the excessive Internet use criteria were involved in this study. Four interventions based on the HAPA model were conducted during 2015–2017. The structural equation model (SEM) was applied to fit the HAPA model.

Results
The rate of average daily time spent online on weekends more than 4 h dropped from 57.2 to 39.1% (P < 0.001). The rate of daily game time more than 2 h decreased from 51.1 to 35.2% (P < 0.001). The result of SEM showed that both the applicability and effectiveness of the HAPA model were well in the intervention of excessive Internet use behaviors with good fitted indicators (χ2/df = 2.066, GFI = 0.889, CFI = 0.938, TLI = 0.928, IFI = 0.938, RMSEA = 0.057). The direct and indirect effects of the main pathways in the HAPA model were statistically significant (P < 0.05). The comparison analysis of HAPA model variables identified that outcome expectancy, intention, maintenance self-efficacy had been improved significantly after interventions.

Conclusion
The intervention measures based on the HAPA model can effectively reduce excessive Internet use behaviors of Chinese rural adolescents, mainly through strengthen outcome expectancy, intention, and maintenance self-efficacy.
Risk of stress/depression and functional impairment in Denmark immediately following a COVID-19 shutdown
Authors: Andersen Lars H. , Fallesen Peter , Bruckner Tim A. 
Published: May 2021

AbstractBackgroundExisting estimates of the impact of the COVID-19 burden on mental wellbeing come from countries with high mortality rates. This study therefore aimed to investigate the impact of the first COVID-19 lockdown (March–April 2020) on risk for stress/depression and functional impairment in a representative sample of adult individuals in Denmark, which had lower infection rates, and whether the impact of lockdown was heterogeneous across living situation.MethodsUsing a representative, randomly drawn sample from the complete Danish adult population interviewed in March 2 to April 13, 2020 (n = 2836) and again in July 2020 (n = 1526, 54% retention rate), we study how the imposed lockdown announced March 11 following the onset of the first Danish wave of COVID-19 infections affected mental wellbeing. We use the World Health Organization Five Well-being Index (WHO-5) and the Work and Social Adjustment Scale (WSAS) to capture risk for stress/depression (WHO-5 < 50) and functional impairment (WSAS > 10). Using covariate adjusted ordinary least squares linear probability models and exploiting variation in the timing of responses occurring just before and just after the introduction of lockdown, we compare respondents before lockdown to respondents that answered during lockdown, as well as to answers in re-interviews in July.ResultsIn our fully controlled models, we find reduced depressive symptoms among adults immediately after the shutdown, concentrated in adults with children living at home (−.089,p < .01 (from pre lockdown baseline .273)). Measures of functional impairment also declined immediately after the March shutdown among adults with children living at home (−.066,p < .05 (from pre lockdown baseline .150)). Impairment intensified for the entire sample between March and July (+.199,p < .001 (from pre lockdown baseline .248)), but depressive symptoms remained at lower rate in July (−.033,p < .05 (from pre lockdown baseline .332).ConclusionsFindings in Denmark indicate that living with children at home may have, in the short term, buffered the potential mental health sequelae of the COVID-19 shutdown.
Re-conceptualizing sustainable urban sanitation in Uganda: why the roots of ‘Slumification’ must be dealt with
Authors: Kwiringira Japheth Nkiriyehe , Kabumbuli Robert , Zakumumpa Henry , Mugisha James , Akugizibwe Mathias , Ariho Paulino , Rujumba Joseph 
Published: May 2021

AbstractBackgroundCountry-wide urbanization in Uganda has continued amidst institutional challenges. Previous interventions in the water and sanitation sector have not addressed the underlying issues of a poorly managed urbanization processes. Poor urbanisation is linked to low productivity, urban poverty, unemployment, limited capacity to plan and offer basic services as well as a failure to enforce urban standards.MethodsThis ethnographic study was carried out in three urban centres of Gulu, Mbarara and Kampala. We explored relationships between urban livelihoods and sustainable urban sanitation, using theeconomic sociology of urban sanitation framework.This framework locates the urbanization narrative within a complex system entailing demand, supply, access, use and sustainability of slum sanitation. We used both inductive and deductive thematic analysis.ResultsMore than any other city in Uganda, Kampala was plagued with poor sanitation services characterized by a mismatch between demand and the available capacity for service provision. Poor slum sanitation was driven by; the need to escape rural poverty through urban migration, urban governance deficits, corruption and the survival imperative, poor service delivery and lack of capacity, pervasive (urban) informality, lack of standards:‘to whom it may concern’attitudes and the normalization of risk as a way of life. Amidst a general lack of affordability, there was a critical lack ofpublic goodconscience. Most urbanites were trapped in poverty, whereby economic survival trumped for the need for meeting desirable sanitation standards.ConclusionsProviding sustainable urban livelihoods and meeting sanitation demands is nested within sustainable livelihoods. Previous interventions have labored to fix the sanitation problem in slums without considering the drivers of this problem. Sustainable urban livelihoods are critical in reducing slums, improving slum living and curtailing the onset ofslumification. Urban authorities need to make urban centres economically vibrant as an integral strategy for attaining better sanitation standards.
Effect of pre-operative internal obturator muscle mass index in MRI on biochemical recurrence of prostate cancer patients after radical prostatectomy: a multi-center study
Authors: Kim Won Tae , Kang Ho Won , Seo Sung Pil , Kim Yong-June , Lee Sang Cheol , Kim Wun-Jae , Cho Bum Sang , Ha Yun Sok , Kwon Tae Gyun , Park Jinsung , Park Seung Chol , Jeong Young Beom , Kang Taek Won , Park Sung-Woo , Yun Seok Joong 
Published: May 2021

Abstract
Background
Recent reports show that the pre-operative or post-operative skeletal mass index (sarcopenia) affects survival rates for various cancers; however, the link between prostate cancer survival and sarcopenia is unclear. Therefore, this study examined the effect of the pre-operative internal obturator muscle (IOM) mass index on biochemical recurrence (BCR) of prostate cancer (PCa) patients who underwent radical prostatectomy.

Methods
In total, 222 patients, who underwent open, laparoscopic, or robot-assisted radical prostatectomy at seven centers in 2011 and were followed up for 5 years, were enrolled. BCR was examined in the context of pre-operative IOM mass index and BMI.

Results
The mean age of the patients was 67.82 ± 6.23 years, and the mean pre-operative prostate-specific antigen (PSA) level was 11.61 ± 13.22 ng/ml. There was no significant difference in baseline characteristics between the low and high IOM mass index groups (p > 0.05). Age, pre-op PSA level, ECE, and T-stage were associated with BCR (p = 0.049, p < 0.001, p = 0.001, p = 0.004, respectively). BMI, prostate volume, Gleason score, resection margin, N-stage, M-stage and IOM mass index was not associated with BCR (p > 0.05).

Conclusions
Pre-operative IOM mass index was not associated with BCR; however, long-term follow-up is necessary to evaluate cancer-specific and overall survival of PCa patients.
Knowledge and attitudes about end-of-life decisions, good death and principles of medical ethics among doctors in tertiary care hospitals in Sri Lanka: a cross-sectional study
Authors: Chang Thashi , Darshani Saumya , Manikavasagam Pavithra , Arambepola Carukshi 
Published: May 2021

Abstract
Background
Competent end-of-life care is an essential component of total health care provision, but evidence suggests that it is often deficient. This study aimed to evaluate the knowledge and attitudes about key end-of-life issues and principles of good death among doctors in clinical settings.

Methods
A cross-sectional study was conducted among allopathic medical doctors working in in-ward clinical settings of tertiary care hospitals in Sri Lanka using a self-administered questionnaire with open- and close-ended questions as well as hypothetical clinical scenarios. Univariate and logistic regression analysis were used to identify the independent factors associated with knowledge and attitudes.

Results
Of the responders who had not been a caregiver for a terminally ill relative (n = 390), 57.9% were men with a mean age of 36.5 years (SD = 8.2). Compared to undergraduate (65.6%; n = 256), only 27.4% (n = 107) had received end-of-life care training at postgraduate level. Only 65.9% of doctors favoured disclosing terminal prognosis to patients; 27.7% of doctors were aware of advance directives; 14.6% were aware of the correct time of death when certifying brain death; 70.3% felt more comfortable in withholding than withdrawing life-sustaining treatment; 61.3% were aware of do-not-attempt cardiopulmonary resuscitation (DNACPR) decisions while 26.7% felt reluctant to administer it; 15.1% thought that all life-sustaining therapy should be withdrawn with a DNACPR decision; and only17.9% were able to name the four principles of medical ethics while 57.9% could not name a single. Participants scored a mean of 9.2 (SD = 3.9) of a maximum 14 points when tested on principles of a ‘good death’. Doctors who had pursued postgraduate studies were more likely to be aware of breaking bad news (adjusted-Odds-Ratio:1.99; 95%CI = 1.19–3.32), advance directives (adjusted-OR: 4.15; 95%CI = 2.49–6.94), aware of certifying the correct time of death (adjusted-OR:2.37; 95%CI = 1.33–4.2) and less reluctant to make DNACPR decisions (adjusted-OR:1.74; 95%CI = 1.13–2.68). Doctors who had worked in ICU were more comfortable withholding than withdrawing treatment (adjusted-OR:1.99; 95%CI = 1.2–3.31).

Conclusions
Knowledge and attitudes about end-of-life care, good death and principles of medical ethics among doctors in Sri Lanka were suboptimal. Structured training of end-of-life care needs to be integrated within curricula and in-service training.
Satisfaction with healthcare services among refugees in Zaatari camp in Jordan
Authors: Salim Nesreen A. , Meyad Shroq Hafedh , Sawair Faleh A. , Satterthwaite Julian D. , Sartawi Samiha 
Published: May 2021

Abstract
Background
Feedback on satisfaction regarding healthcare services is vital for continuous improvement of the service delivery process and outcome.

Aims and methods
The objective of this study was to assess the satisfaction of refugees with the medical and dental services in Zaatari camp, under 3 domains with 20 key indicators (human and physical health resources, interaction and reactivity, and administration) using a self-administered questionnaire.

Results
Of the 500 participants, the satisfaction rate was 72.5%. Young participants and participants with a shorter stay in the camp showed higher overall satisfaction rates (P ≤ 0.01). Within the domains, ‘interaction and reactivity’ achieved the highest satisfaction score, whereas ‘administration efficiency’ was ranked the lowest. As for elements within the domains, the most acceptable were the sufficient number of staff and the working hours, availability of radiological services and proper care for children, reasonable waiting time and asking for medical history in every visit. Whereas difficulty to access healthcare services, difficulty to be referred to hospitals, lack of follow up and lack of dental services were the least acceptable.

Conclusion
In conclusion, whereas refugees were generally satisfied with the provided services, this study indicates that there are areas for further service improvement. This study highlights a significant gaps in healthcare services which if not addressed have the potential to amplify oral/medical health problems.