bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional status and its associated factors among community-dwelling older adults in rural Nepal: findings from a cross-sectional study
Authors: Ghimire Saruna , Paudel Grish , Mistry Sabuj Kanti , Parvez Mahmood , Rayamajhee Binod , Paudel Pravash , Tamang Man Kumar , Yadav Uday Narayan 
Published: May 2021

Abstract
Background
The high burden of chronic conditions, coupled with various physical, mental, and psychosocial changes that accompany the phenomenon of aging, may limit the functional ability of older adults. This study aims to assess the prevalence of poor functional status and investigate factors associated with poor functional status among community-dwelling older adults in rural communities of eastern Nepal.

Methods
Data on 794 older adults aged ≥ 60 years from a previous community-based cross-sectional study was used. Participants were recruited from rural municipalities of Morang and Sunsari districts of eastern Nepal using multi-stage cluster sampling. Functional status was assessed in terms of participants’ ability to perform activities of daily living using the Barthel Index. Covariates included sociodemographic characteristics, lifestyle factors, and self-reported chronic conditions. A binary logistic regression model was used to investigate factors associated with poor functional status.

Results
The overall prevalence of poor functional status was 8.3 % (male: 7.0 % and female: 9.6 %), with most dependence noted for using stairs (17.3 %), followed by dressing (21.9 %) on Barthel Index. In the adjusted model, oldest age group (odds ratio [OR] = 2.83, 95 %CI: 1.46, 5.50), those unemployed (OR = 2.41, 95 %CI: 1.26, 4.65), having memory/concentration problems (OR = 2.32, 95 %CI: 1.30, 4.13), depressive symptoms (OR = 2.52, 95 %CI: 1.28, 4.95), and hypertension (OR = 1.78, 95 %CI: 1.03, 3.06) had almost or more than two times poor functioning.

Conclusions
One in 12 older adults had poor functional status as indicated by their dependency on the items of the Barthel Index; those in the oldest age bracket were more likely to exhibit poor functional status. We suggest future studies from other geographies of the country to supplement our study from the rural setting for comprehensive identification of the problem, which could guide the development of prevention strategies and comprehensive interventions for addressing the unmet needs of the older adults for improving functional status.
Transcriptome analysis of potential candidate genes and molecular pathways in colitis-associated colorectal cancer of Mkp-1-deficient mice
Authors: Hammad Ahmed , Zheng Zhao-Hong , Namani Akhileshwar , Elshaer Mohamed , Wang Xiu Jun , Tang Xiuwen 
Published: May 2021

Abstract
Background
The nuclear phosphatase mitogen-activate protein kinase phosphatase-1 (MKP-1) is a key negative regulator of the innate immune response through the regulation of the biosynthesis of proinflammatory cytokines. In colorectal cancer (CRC), which is induced mainly by chronic inflammation, Mkp-1 overexpression was found in addition to disturbances in Mkp-1 functions, which may play a role in cancer development in different types of tumors. However, the potential molecular mechanisms by which Mkp-1 influences CRC development is not clear. Here, we performed global gene expression profiling of Mkp-1 KO mice using RNA sequencing (RNA-seq) to explore the role of Mkp-1 in CRC progression using transcriptome analysis.

Methods
Azoxymethane/dextran sodium sulfate (AOM/DSS) mouse models were used to examine the most dramatic molecular and signaling changes that occur during different phases of CRC development in wild-type mice and Mkp-1 KO mice. Comprehensive bioinformatics analyses were used to elucidate the molecular processes regulated by Mkp-1. Differentially expressed genes (DEGs) were identified and functionally analyzed by Gene Ontology (GO), Kyoto Enrichment of Genes and Genomes (KEGG). Then, protein-protein interaction (PPI) network analysis was conducted using the STRING database and Cytoscape software.

Results
Persistent DEGs were different in adenoma and carcinoma stage (238 & 251, respectively) and in WT and MKp-1 KO mice (221& 196, respectively). Mkp-1 KO modulated key molecular processes typically activated in cancer, in particular, cell adhesion, ion transport, extracellular matrix organization, response to drug, response to hypoxia, and response to toxic substance. It was obvious that these pathways are closely associated with cancer development and metastasis. From the PPI network analyses, nine hub genes associated with CRC were identified.

Conclusion
These findings suggest that MKp-1 and its hub genes may play a critical role in cancer development, prognosis, and determining treatment outcomes. We provide clues to build a potential link between Mkp-1 and colitis-associated tumorigenesis and identify areas requiring further investigation.

Graphical abstract
Measuring the global, regional, and national burden of multiple myeloma from 1990 to 2019
Authors: Zhou Linghui , Yu Qin , Wei Guoqing , Wang Linqin , Huang Yue , Hu Kejia , Hu Yongxian , Huang He 
Published: May 2021

Abstract
Background
Multiple myeloma (MM) is a major health concern. Understanding the different burden and tendency of MM in different regions is crucial for formulating specific local strategies. Therefore, we evaluated the epidemiologic patterns and explored the risk factors for MM death.

Methods
Data on MM were collected from the 2019 Global Burden of Disease study. We used incidence, mortality, and disability adjusted life-years to estimate the global, regional, and national burden of MM.

Results
In 2019, there were 155,688 (95% UI, 136,585 – 172,577) MM cases worldwide, of which 84,516 (54.3%, 70,924 – 94,910) were of men. The age-standardized incidence rate (ASIR) was 1.72/100,000 persons (95% UI, 1.59–1.93) in 1990 and 1.92/100,000 persons (95% UI, 1.68–2.12) in 2019. The number of MM deaths increased 1.19-fold from 51,862 (95% UI, 47,710–58,979) in 1990 to 113,474 (95% UI, 99,527 – 121,735) in 2019; the age-standardized death rate (ASDR) was 1.42/100,000 persons (95% UI, 1.24–1.52) in 2019. In recent 15 years, ASDR showed a steady tendency for men, and a downward tendency for women. Countries with high social-demographic indexes exhibited a higher ASIR and ASDR. Australasia, North America, and Western Europe had the highest ASIR and ASDR, with 46.3% incident cases and 41.8% death cases. Monaco had the highest ASIR and ASDR, which was almost half as high as the second highest country Barbados. In addition, United Arab Emirates and Qatar had the largest growth multiple in ASIR and ASDR, which was twice the third country Djibouti.

Conclusions
Globally, incident and death MM cases have more than doubled over the past 30 years. The increasing global burden may continue with population aging, whereas mortality may continue to decrease with the progression of medical technology. The global burden pattern of MM was diverse, therefore specific local strategies based on different burden patterns for MM are necessary.
Incidence trends in bladder and lung cancers between Denmark, Finland and Sweden may implicate oral tobacco (snuff/snus) as a possible risk factor
Authors: Hemminki Kari , Försti Asta , Hemminki Akseli , Ljungberg Börje , Hemminki Otto 
Published: May 2021

Abstract
Background
The dominant risk factor for urinary bladder cancer has been cigarette smoking, but, as smoking prevalence is decreasing in many populations, other risk factors may become uncovered. Such new risk factors could be responsible for halting the declining incidence of bladder cancer. We hypothesize that snuff use by Swedish men may increase the rate for bladder cancer, as snuff contains carcinogenic nitrosamines.

Methods
We carried out an ecological study by comparing incidence trends in lung and bladder cancers between Danish, Finnish and Swedish men in order to test if the Swedish bladder cancer rate deviates from the Danish and Finnish ones. We used the NORDCAN database for cancer data from 1960 through 2016 to test the hypothesis.

Results
In the three countries, the incidence of lung cancer started to decrease after a peak incidence, and this was later followed by declining incidence in bladder cancer in Denmark from 1990 to 2016 by 14.3%, in Finland by 8.3% but not in Sweden (the decline of 1.4% was not significant). The difference in trends can be partly explained by the increasing incidence in Swedish men aged 70 or more years. Sweden differs from the two other countries by low male smoking prevalence but increasing use of snuff recorded by various surveys.

Conclusion
The stable bladder cancer trend for Swedish men was opposite to the declining trends in Denmark, Finland and globally. We suggest that this unusual finding may be related to the increasing use of snuff by Swedish men. Average users of snuff are exposed to at least 3 times higher levels of carcinogenic tobacco-specific nitrosamines than a smoker of one daily pack of cigarettes.
DNA methylation signatures associated with prognosis of gastric cancer
Authors: Dai Jin , Nishi Akihiro , Li Zhe-Xuan , Zhang Yang , Zhou Tong , You Wei-Cheng , Li Wen-Qing , Pan Kai-Feng 
Published: May 2021

Abstract
Background
Few studies have examined prognostic outcomes-associated molecular signatures other than overall survival (OS) for gastric cancer (GC). We aimed to identify DNA methylation biomarkers associated with multiple prognostic outcomes of GC in an epigenome-wide association study.

Methods
Based on the Cancer Genome Atlas (TCGA), DNA methylation loci associated with OS (n = 381), disease-specific survival (DSS, n = 372), and progression-free interval (PFI, n = 383) were discovered in training set subjects (false discovery rates < 0.05) randomly selected for each prognostic outcome and were then validated in remaining subjects (P-values < 0.05). Key CpGs simultaneously validated for OS, DSS, and PFI were further assessed for disease-free interval (DFI, n = 247). Gene set enrichment analyses were conducted to explore the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways simultaneously enriched for multiple GC prognostic outcomes. Methylation correlated blocks (MCBs) were identified for co-methylation patterns associated with GC prognosis. Based on key CpGs, risk score models were established to predict four prognostic outcomes. Spearman correlation analyses were performed between key CpG sites and their host gene mRNA expression.

Results
We newly identified DNA methylation of seven CpGs significantly associated with OS, DSS, and PFI of GC, including cg10399824 (GRK5), cg05275153 (RGS12), cg24406668 (MMP9), cg14719951(DSC3), and cg25117092 (MED12L), and two in intergenic regions (cg11348188 and cg11671115). Except cg10399824 and cg24406668, five of them were also significantly associated with DFI of GC. Neuroactive ligand-receptor interaction pathway was suggested to play a key role in the effect of DNA methylation on GC prognosis. Consistent with individual CpG-level association, three MCBs involving cg11671115, cg14719951, and cg24406668 were significantly associated with multiple prognostic outcomes of GC. Integrating key CpG loci, two risk score models performed well in predicting GC prognosis. Gene body DNA methylation of cg14719951, cg10399824, and cg25117092 was associated with their host gene expression, whereas no significant associations between their host gene expression and four clinical prognostic outcomes of GC were observed.

Conclusions
We newly identified seven CpGs associated with OS, DSS, and PFI of GC, with five of them also associated with DFI, which might inform patient stratification in clinical practices.
Risk factors associated with scabies infestation among primary schoolchildren in a low socio-economic area in southeast of Iran
Authors: Sanei-Dehkordi Alireza , Soleimani-Ahmadi Moussa , Zare Mehdi , Jaberhashemi Seyed Aghil 
Published: May 2021

Abstract
Background
Scabies is a neglected tropical disease caused by the mite Sarcoptes scabiei that burrows under the skin. It is a major health problem in tropical areas, largely affecting children. Scabies is common and highly contagious and in schoolchildren spreads quite rapidly, due to overcrowding and close contact within the schools. This study aimed to determine the risk factors associated with scabies infestation among primary schoolchildren in Bashagard County, one of the low socio-economic areas in southeast of Iran.

Methods
To conduct this community-based, descriptive, and cross-sectional study, four primary schools were randomly selected in the Bashagard County. All students in these schools were selected and examined for scabies. Clinical examination and sociodemographic profile of students were assessed using a pre-tested structured questionnaire. Chi-square test, and binary logistic regression were used to analyse the factors associated with scabies infestation by SPSS version 21 software.

Results
Out of 480 studied schoolchildren, 15 cases of scabies with a prevalence of 3.1 % were observed. The frequency of infestation in males was 1.6 % and it was 4.7 % in females. Independent factors associated with a high risk of scabies infestation in unadjusted analysis were being student of grade 5–6 (cOR = 13.12, 95 % CI 2.92–58.89, p = 0.0001), low educational level of father (cOR = 4.37, 95 % CI 0.97–19.59, p = 0.036), low educational level of mother (cOR = 4.14, 95 % CI 1.92–18.57, p = 0.045), joblessness of father (cOR = 14.77, 95 % CI 4.97–43.89, p = 0.0001), employment of mother (cOR = 5.28, 95 % CI 1.38–20.16, p = 0.007), large family size (cOR = 3.34, 95 % CI 1.05–10.64, p = 0.031), use of shared articles (cOR = 33.37, 95 % CI 10.82–102.90, p = 0.0001), and absence of bathroom in the house (cOR = 11.77, 95 % CI 2.16–63.94, p = 0.0001).

Conclusions
Results of this study confirmed that scabies is still one of the most important health problems in the primary schools of the Bashagard County. Low socioeconomic status and personal hygiene of the schoolchildren were the most important factors influencing the prevalence of scabies. Improvement of socioeconomic conditions and implementation of appropriate educational programs and active surveillance system to quickly detect and treat scabies cases are necessary in order to reduce the prevalence of scabies in schoolchildren in this area.
High cytotoxicity of betulin towards fish and murine fibroblasts: Is betulin safe for nonneoplastic cells?
Authors: Małaczewska Joanna , Kaczorek-Łukowska Edyta , Kazuń Barbara 
Published: May 2021

Abstract
Background
Betulin, a natural pentacyclic triterpene with the lupane structure that is present in significant amounts in the outer bark of birch, is known for its broad array of biological and pharmacological properties. Betulin has attracted attention as a potential, natural-origin antimicrobial substance. The literature describes it as selectively toxic to neoplastic cells but safe for normal cells.
The research aim was to evaluate the basal cytotoxicity of betulin towards fish (BF-2) and murine (NIH/3T3) fibroblasts. We used four colorimetric tests that provide a preliminary evaluation of possible mechanisms of the cytotoxicity of a compound to assess the degree of the toxicity of betulin after 24, 48 and 72 h of incubation with cells: the MTT assay (mitochondrial activity assessment), the NRU assay (lysosomal membrane integrity assessment), the LDH assay (cellular membrane integrity assessment) and the SRB assay (total cellular protein content determination).

Results
The results revealed an exceptionally high sensitivity of mitochondria to the effect of betulin, with the other endpoints being less sensitive. Although murine fibroblasts were more vulnerable to the toxic effect of betulin than fish fibroblasts, the betulin CC50 values for both cell lines were comparable with analogous IC50 values determined by other researchers in studies involving cancerous cells.

Conclusions
The results indicate the need to verify the claim about the selective toxicity of betulin towards malignant cells and to conduct safety/toxicity tests before any potential therapeutic use of betulin in veterinary medicine.
Long non-coding RNAs in Epstein–Barr virus-related cancer
Authors: Liu Yitong , Hu Zhizhong , Zhang Yang , Wang Chengkun 
Published: May 2021

AbstractEpstein Barr-virus (EBV) is related to several cancers. Long non-coding RNAs (lncRNAs) act by regulating target genes and are involved in tumourigenesis. However, the role of lncRNAs in EBV-associated cancers is rarely reported. Understanding the role and mechanism of lncRNAs in EBV-associated cancers may contribute to diagnosis, prognosis and clinical therapy in the future. EBV encodes not only miRNAs, but also BART lncRNAs during latency and the BHLF1 lncRNA during both the latent and lytic phases. These lncRNAs can be targeted regulate inflammation, invasion, and migration and thus tumourigenesis. The products of EBV also directly and indirectly regulate host lncRNAs, including LINC00312, NORAD CYTOR, SHNG8, SHNG5, MINCR, lncRNA-BC200, LINC00672, MALATI1, LINC00982, LINC02067, IGFBP7‐AS1, LOC100505716, LOC100128494, NAG7 and RP4-794H19.1, to facilitate tumourigenesis using different mechanisms. Additionally, lncRNAs have been previously validated to interact with microRNAs (miRNAs), and lncRNAs and miRNAs mutually suppress each other. The EBV-miR-BART6-3p/LOC553103/STMN1 axis inhibits EBV-associated tumour cell proliferation. Additionally, H. pylori–EBV co-infection promotes inflammatory lesions and results in EMT. HPV–EBV co-infection inhibits the transition from latency to lytic replication. KSHV–EBV co-infection aggravates tumourigenesis in huNSG mice. COVID-19–EBV co-infection may activate the immune system to destroy a tumour, although this situation is rare and the mechanism requires further confirmation. Hopefully, this information will shed some light on tumour therapy strategies tumourigenesis. Additionally, this strategy benefits for infected patients by preventing latency to lytic replication. Understanding the role and expression of lnRNAs in these two phases of EBV is critical to control the transition from latency to the lytic replication phase. This review presents differential expressed lncRNAs in EBV-associated cancers and provides resources to aid in developing superior strategies for clinical therapy.
Sharing power in global health research: an ethical toolkit for designing priority-setting processes that meaningfully include communities
Authors: Pratt Bridget 
Published: May 2021

AbstractTo promote social justice and equity, global health research should meaningfully engage communities throughout projects: from setting agendas onwards. But communities, especially those that are considered disadvantaged or marginalised, rarely have a say in the priorities of the research projects that aim to help them. So far, there remains limited ethical guidance and resources on how to share power with communities in health research priority-setting. This paper presents an“ethical toolkit”for academic researchers and their community partners to use to design priority-setting processes that meaningfully include the communities impacted by their projects. An empirical reflective equilibrium approach was employed to develop the toolkit. Conceptual work articulated ethical considerations related to sharing power in g0l0o0bal health research priority-setting, developed guidance on how to address them, and created an initial version of the toolkit. Empirical work (51 in-depth interviews, 1 focus group, 2 case studies in India and the Philippines) conducted in 2018 and 2019 then tested those findings against information from global health research practice. The final ethical toolkit is a reflective project planning aid. It consists of 4 worksheets (Worksheet 1- Selecting Partners; Worksheet 2- Deciding to Partner; Worksheet 3- Deciding to Engage with the Wider Community; Worksheet 4- Designing Priority-setting) and a Companion Document detailing how to use them. Reflecting on and discussing the questions in Worksheets 1 to 4 before priority-setting will help deliver priority-setting processes that share power with communities and projects with research topics and questions that more accurately reflect their healthcare and system needs.
An analysis of the impact of newborn survival policies in Pakistan using a policy triangle framework
Authors: Ahmed Jamil , Schneider Carmen Huckel , Alam Ashraful , Raynes-Greenow Camille 
Published: May 2021

Introduction
Pakistan has made slow progress towards reducing the newborn mortality burden; as a result, it has the highest burden of newborn mortality worldwide. This article presents an analysis of the current policies, plans, and strategies aimed at reducing the burden of newborn death in Pakistan for the purpose of identifying current policy gaps and contextual barriers towards proposing policy solutions for improved newborn health.

Methods
We begin with a content analysis of federal-level policies that address newborn mortality within the context of health system decentralization over the last 20 years. This is then followed by a case study analysis of policy and programme responses in a predominantly rural province of Pakistan, again within the context of broader health system decentralization. Finally, we review successful policies in comparable countries to identify feasible and effective policy choices that hold promise for implementation in Pakistan, considering the policy constraints we have identified.

Results
The major health policies aimed at reduction of newborn mortality, following Pakistan’s endorsement of global newborn survival goals and targets, lacked time-bound targets. We found confusion around roles and responsibilities of institutions in the implementation process and accountability for the outcomes, which was exacerbated by an incomplete decentralization of healthcare policy-making and health service delivery, particularly for women around birth, and newborns. Such wide gaps in the areas of target-setting, implementation mechanism, and evaluation could be because the policy-making largely ignored international commitments and lessons of successful policy-making in comparable regional counties.

Conclusions
Inclusion of clear goals and targets in newborn survival policies and plans, completion of the decentralization process of maternal and child healthcare service delivery, and policy-making and implementation by translating complex evidence and using regional but locally applicable case studies will be essential to any effective policy-making on newborn survival in Pakistan.