bluuebunny/crossref_metadata_2025_split huggingface dataset:
Still engaged – healthcare staff’s engagement when introducing a new eHealth solution for wound management: a qualitative study
Authors: Fagerström Cecilia , Wickström Hanna , Tuvesson Hanna 
Published: January 2022

AbstractBackgroundeHealth solutions have often been considered favourable for improved effectiveness and quality in healthcare services for wound management. Staff engagement related to organisational changes is a key factor for successful development and implementation of a new eHealth solution, like a digital decision support systems (DDSS). It is essential to understand the engagement process in terms of sustainability, wellbeing in staff and efficiency in a long-term perspective. The aim of this study was to describe healthcare staff’s engagement during a 6-month test of an eHealth solution (DDSS) for wound management.MethodsA qualitative design, including interviews conducted with healthcare staff working with wound management within primary, community and specialist care (n = 11) on two occasions: at the introduction of the solution and after 6 months, when the test period was over. Data were interpreted with qualitative content analysis.ResultsHealthcare staff’s descriptions from a 6-month test of an eHealth solution for wound management can be summarised asEngaging through meaning, but draining. The analysis revealed a result with three subcategories:Having a shared interest is stimulating, Good but not perfectandExciting, but sometimes exhausting.The staff described their engagement as sustained through feelings of meaningfulness when using the eHealth solution, but limited by feelings of exhaustion due to heavy workload and lack of support and understanding from others.ConclusionsThe results indicate that the healthcare staff who tested the eHealth solution described themselves as individuals who easily become engaged when an idea and efforts felt meaningful. The staff needed resources to nourish engagement in their new role when implementing eHealth in the clinical everyday work of wound management. Allocating time and support are important to consider when planning for sustainable implementation of eHealth solutions in healthcare organisations.
Variability in newborn telomere length is explained by inheritance and intrauterine environment
Authors: Chen Li , Tan Karen Mei Ling , Gong Min , Chong Mary F. F. , Tan Kok Hian , Chong Yap Seng , Meaney Michael J. , Gluckman Peter D. , Eriksson Johan G. , Karnani Neerja 
Published: January 2022

Abstract
Background
Telomere length (TL) and its attrition are important indicators of physiological stress and biological aging and hence may vary among individuals of the same age. This variation is apparent even in newborns, suggesting potential effects of parental factors and the intrauterine environment on TL of the growing fetus.

Methods
Average relative TLs of newborns (cord tissue, N = 950) and mothers (buffy coat collected at 26–28 weeks of gestation, N = 892) were measured in a birth cohort. This study provides a comprehensive analysis of the effects of heritable factors, socioeconomic status, and in utero exposures linked with maternal nutrition, cardiometabolic health, and mental well-being on the newborn TL. The association between maternal TL and antenatal maternal health was also studied.

Results
Longer maternal TL (β = 0.14, P = 1.99E−05) and higher paternal age (β = 0.10, P = 3.73E−03) were positively associated with newborn TL. Genome-wide association studies on newborn and maternal TLs identified 6 genetic variants in a strong linkage disequilibrium on chromosome 3q26.2 (Tag SNP-LRRC34-rs10936600: Pmeta = 5.95E−08). Mothers with higher anxiety scores, elevated fasting blood glucose, lower plasma insulin-like growth factor-binding protein 3 and vitamin B12 levels, and active smoking status during pregnancy showed a higher risk of giving birth to offspring with shorter TL. There were sex-related differences in the factors explaining newborn TL variation. Variation in female newborn TL was best explained by maternal TL, mental health, and plasma vitamin B12 levels, while that in male newborn TL was best explained by paternal age, maternal education, and metabolic health. Mother’s TL was associated with her own metabolic health and nutrient status, which may have transgenerational effects on offspring TL.

Conclusions
Our findings provide a comprehensive understanding of the heritable and environmental factors and their relative contributions to the initial setting of TL and programing of longevity in early life. This study provides valuable insights for preventing in utero telomere attrition by improving the antenatal health of mothers via targeting the modifiable factors.

Trial registration
ClinicalTrials.gov, NCT01174875. Registered on 1 July 2010
The diagnosis and molecular epidemiology investigation of avian hepatitis E in Shandong province, China
Authors: Liu Kuihao , Zhao Yiran , Zhao Jun , Geng Ningwei , Meng Fanliang , Wang Siqi , Li Jing , Zhong Zhaobing , Zhu Liya , Liu Sidang , Li Ning 
Published: January 2022

Abstract
Background
Avian hepatitis E virus (HEV) is the pathogenic agent of big liver and spleen disease (BLS) and of hepatitis-splenomegaly syndrome (HSS) in chickens, which have caused economic losses to the poultry industry in China. In this study, 18 samples of BLS chickens were collected to reveal the molecular epidemiological characteristics of avian HEV in the province of Shandong, China.

Results
Gross and microscopic lesions of clinical samples were observed; then, virology detection and genetic analysis of avian HEV were performed. The results showed that there was significant swelling and rupture in the liver and that the spleen was enlarged. Microscopic lesions demonstrated obvious hemorrhage in the liver, with infiltration of heterophilic granulocytes, lymphocytes, and macrophages, as well as the reduction of lymphocytes in the spleen. Eleven of the 18 samples were positive for avian HEV, with a positive rate of 61.11%. More importantly, all avian HEV-positive samples were mixed infections: among these, the mixed infections of avian HEV and chicken infectious anemia virus (CIAV) and avian HEV and fowl adenovirus (FAdV) were the most common. Furthermore, the genetic evolution analysis showed that all avian HEV strains obtained here did not belong to the reported 4 genotypes, thus constituting a potential novel genotype.

Conclusions
These results of this study further enrich the epidemiological data on avian HEV in Shandong, prove the genetic diversity of avian HEV in China, and uncover the complex mixed infections of avian HEV clinical samples.
Exosome-liposome hybrid nanoparticle codelivery of TP and miR497 conspicuously overcomes chemoresistant ovarian cancer
Authors: Li Longxia , He Di , Guo Qianqian , Zhang Zhiyoung , Ru Dan , Wang Liting , Gong Ke , Liu Fangfang , Duan Yourong , Li He 
Published: January 2022

AbstractBackgroundAlthough cisplatin-based chemotherapy has been used as the first-line treatment for ovarian cancer (OC), tumor cells develop resistance to cisplatin during treatment, causing poor prognosis in OC patients. Studies have demonstrated that overactivation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway is involved in tumor chemoresistance and that overexpression of microRNA-497 (miR497) may overcome OC chemotherapy resistance by inhibiting the mTOR pathway. However, the low transcriptional efficiency and unstable chemical properties of miR497 limit its clinical application. Additionally, triptolide (TP) was confirmed to possess a superior killing effect on cisplatin-resistant cell lines, partially through inhibiting the mTOR pathway. Even so, the clinical applications of TP are restricted by serious systemic toxicity and weak water solubility.ResultsHerein, whether the combined application of miR497 and TP could further overcome OC chemoresistance by synergically suppressing the mTOR signaling pathway was investigated. Bioinspired hybrid nanoparticles formed by the fusion of CD47-expressing tumor exosomes and cRGD-modified liposomes (miR497/TP-HENPs) were prepared to codeliver miR497 and TP. In vitro results indicated that the nanoparticles were efficiently taken up by tumor cells, thus significantly enhancing tumor cell apoptosis. Similarly, the hybrid nanoparticles were effectively enriched in the tumor areas and exerted significant anticancer activity without any negative effects in vivo. Mechanistically, they promoted dephosphorylation of the overactivated PI3K/AKT/mTOR signaling pathway, boosted reactive oxygen species (ROS) generation and upregulated the polarization of macrophages from M2 to M1 macrophages.ConclusionOverall, our findings may provide a translational strategy to overcome cisplatin-resistant OC and offer a potential solution for the treatment of other cisplatin-resistant tumors.Graphical Abstract
The PB1 gene from H9N2 avian influenza virus showed high compatibility and increased mutation rate after reassorting with a human H1N1 influenza virus
Authors: Cui Hongrui , Che Guangsheng , de Jong Mart C. M. , Li Xuesong , Liu Qinfang , Yang Jianmei , Teng Qiaoyang , Li Zejun , Beerens Nancy 
Published: January 2022

Abstract
Background
Reassortment between human and avian influenza viruses (AIV) may result in novel viruses with new characteristics that may threaten human health when causing the next flu pandemic. A particular risk may be posed by avian influenza viruses of subtype H9N2 that are currently massively circulating in domestic poultry in Asia and have been shown to infect humans. In this study, we investigate the characteristics and compatibility of a human H1N1 virus with avian H9N2 derived genes.

Methods
The polymerase activity of the viral ribonucleoprotein (RNP) complex as combinations of polymerase-related gene segments derived from different reassortment events was tested in luciferase reporter assays. Reassortant viruses were generated by reverse genetics. Gene segments of the human WSN-H1N1 virus (A/WSN/1933) were replaced by gene segments of the avian A2093-H9N2 virus (A/chicken/Jiangsu/A2093/2011), which were both the Hemagglutinin (HA) and Neuraminidase (NA) gene segments in combination with one of the genes involved in the RNP complex (either PB2, PB1, PA or NP). The growth kinetics and virulence of reassortant viruses were tested on cell lines and mice. The reassortant viruses were then passaged for five generations in MDCK cells and mice lungs. The HA gene of progeny viruses from different passaging paths was analyzed using Next-Generation Sequencing (NGS).

Results
We discovered that the avian PB1 gene of H9N2 increased the polymerase activity of the RNP complex in backbone of H1N1. Reassortant viruses were able to replicate in MDCK and DF1 cells and mice. Analysis of the NGS data showed a higher substitution rate for the PB1-reassortant virus. In particular, for the PB1-reassortant virus, increased virulence for mice was measured by increased body weight loss after infection in mice.

Conclusions
The higher polymerase activity and increased mutation frequency measured for the PB1-reassortant virus suggests that the avian PB1 gene of H9N2 may drive the evolution and adaptation of reassortant viruses to the human host. This study provides novel insights in the characteristics of viruses that may arise by reassortment of human and avian influenza viruses. Surveillance for infections with H9N2 viruses and the emergence of the reassortant viruses in humans is important for pandemic preparedness.
The evaluation of podiatrists, with knowledge and training in diagnostic musculoskeletal ultrasound, to describe sonographic images of diabetic foot wounds in the United Kingdom and Australia
Authors: Dando Charlotte , Lane Georgia , Bowen Catherine , Henshaw Frances 
Published: January 2022

AbstractAimsCurrently, wound management decisions are based largely on visual observations such as photographs, descriptors or measurements which can lack detail and do not always capture the sub‐wound area. A previous case series suggests that there is benefit in using ultrasound imaging (USI) to evaluate diabetic foot ulcers (DFU) at point‐of‐care, however no guidance exists to inform its use. This scoping exercise explores the capacity of podiatrists with experience in interpreting musculoskeletal structures using USI to interpret sonographic images of DFU.MethodsFollowing a short briefing session, podiatrists with previous musculoskeletal (MSK) USI training were asked to review and report on previously recorded static sonographic images (n = 8) of active DFU. Content analysis was utilised to identify recurring keywords within the podiatrists' reports which were coded and assigned to categories to gain context to the data.ResultsSeven podiatrists participated in the study. Four categories were constructed for the purposes of analysis:

Frequency of reporting, 2) Language used in reporting, 3) Observations, 4) Clinical impression
Frequently, the reported findings between podiatrists were found to be similar, especially those related to bone morphology. However greater variability was seen in the reporting of wound specific soft‐tissue observations.ConclusionThis scoping exercise has shown that podiatrists can translate their existing USI skills to make rudimentary reports on clinical findings in DFU. All participants were consistently able to identify and describe characteristics associated with DFU from a single b mode static wound ultrasound image. Findings from this investigation can be used as a foundation for further work to establish accuracy and reliability to validate DFU sonography. In conjunction the development of protocols and training materials will enable the adoption of USI to assess DFU in clinical practice. This will in turn, contribute to improved patient care and establish a new paradigm for wound surveillance which is translatable to other wound types.
Neuropilin-1 is over-expressed in claudin-low breast cancer and promotes tumor progression through acquisition of stem cell characteristics and RAS/MAPK pathway activation
Authors: Tang Yu Hin , Rockstroh Anja , Sokolowski Kamil A. , Lynam Layla-Rose , Lehman Melanie , Thompson Erik W. , Gregory Philip A. , Nelson Colleen C. , Volpert Marianna , Hollier Brett G. 
Published: January 2022

Abstract
Background
Triple-negative breast cancers (TNBC) have a relatively poor prognosis and responses to targeted therapies. Between 25 and 39% of TNBCs are claudin-low, a poorly differentiated subtype enriched for mesenchymal, stem cell and mitogen-activated signaling pathways.
We investigated the role of the cell-surface co-receptor NRP1 in the biology of claudin-low TNBC.

Methods
The clinical prognostic value of NRP1 was determined by Kaplan–Meier analysis. GSVA analysis of METABRIC and Oslo2 transcriptomics datasets was used to correlate NRP1 expression with claudin-low gene signature scores. NRP1 siRNA knockdown was performed in MDA-MB-231, BT-549, SUM159 and Hs578T claudin-low cells and proliferation and viability measured by live cell imaging and DNA quantification. In SUM159 orthotopic xenograft models using NSG mice, NRP1 was suppressed by shRNA knockdown or systemic treatment with the NRP1-targeted monoclonal antibody Vesencumab. NRP1-mediated signaling pathways were interrogated by protein array and Western blotting.

Results
High NRP1 expression was associated with shorter relapse- and metastasis-free survival specifically in ER-negative BrCa cohorts. NRP1 was over-expressed specifically in claudin-low clinical samples and cell lines, and NRP1 knockdown reduced proliferation of claudin-low cells and prolonged survival in a claudin-low orthotopic xenograft model. NRP1 inhibition suppressed expression of the mesenchymal and stem cell markers ZEB1 and ITGA6, respectively, compromised spheroid-initiating capacity and exerted potent anti-tumor effects on claudin-low orthotopic xenografts (12.8-fold reduction in endpoint tumor volume). NRP1 was required to maintain maximal RAS/MAPK signaling via EGFR and PDGFR, a hallmark of claudin-low tumors.

Conclusions
These data implicate NRP1 in the aggressive phenotype of claudin-low breast cancer and offer a novel targeted therapeutic approach to this poor prognosis subtype.
LncRNA IPW inhibits growth of ductal carcinoma in situ by downregulating ID2 through miR-29c
Authors: Deshpande Ravindra Pramod , Sharma Sambad , Liu Yin , Pandey Puspa Raj , Pei Xinhong , Wu Kerui , Wu Shih-Ying , Tyagi Abhishek , Zhao Dan , Mo Yin-Yuan , Watabe Kounosuke 
Published: January 2022

Abstract
Background
Ductal carcinoma in situ (DCIS) of breast is the noninvasive lesion that has propensity to progress to the malignant form. At present, it is still unknown which lesions can potentially progress to invasive forms. In this study, we aimed to identify key lncRNAs involved in DCIS growth.

Methods
We employ disease-related lncProfiler array to identify IPW in specimens of DCIS and matching control samples and validate the observations in three DCIS-non-tumorigenic cell lines. Further, we examine the mechanism of IPW action and the downstream signaling in in vitro and in vivo assays. Importantly, we screened a library containing 390 natural compounds to identify candidate compound selectively inhibiting IPW low DCIS cells.

Results
We identified lncRNA IPW as a novel tumor suppressor critical for inhibiting DCIS growth. Ectopic expression of IPW in DCIS cells strongly inhibited cell proliferation, colony formation and cell cycle progression while silencing IPW in primary breast cells promoted their growth. Additionally, orthotropic implantation of cells with ectopic expression of IPW exhibited decreased tumor growth in vivo. Mechanistically, IPW epigenetically enhanced miR-29c expression by promoting H3K4me3 enrichment in its promoter region. Furthermore, we identified that miR-29c negatively regulated a stemness promoting gene, ID2, and diminished self-renewal ability of DCIS cells. Importantly, we screened a library containing 390 natural compounds and identified toyocamycin as a compound that selectively inhibited the growth of DCIS with low expression of IPW, while it did not affect DCIS with high IPW expression. Toyocamycin also suppressed genes associated with self-renewal ability and inhibited DCIS growth in vivo.

Conclusion
Our findings revealed a critical role of the IPW-miR-29c-ID2 axis in DCIS formation and suggested potential clinical use of toyocamycin for the treatment of DCIS.
Microbiota of the prostate tumor environment investigated by whole-transcriptome profiling
Authors: Salachan Paul Vinu , Rasmussen Martin , Fredsøe Jacob , Ulhøi Benedicte , Borre Michael , Sørensen Karina Dalsgaard 
Published: January 2022

AbstractBackgroundWith over 350,000 estimated deaths worldwide in 2018, prostate cancer (PCa) continues to be a major health concern and a significant cause of cancer-associated mortality among men. While cancer in general is considered a disease of the human genome, there is a growing body of evidence suggesting that changes to the healthy microbiota could play a vital role in cancer development, progression, and/or treatment outcome.MethodsUsing a metatranscriptomic approach, we annotated the microbial reads obtained from total RNA sequencing of 106 prostate tissue samples from 94 PCa patients (discovery cohort). We investigated microbial dysbiosis associated with PCa by systematically comparing the microbiomes between benign and malignant tissue samples, between less vs. more-aggressive PCa, and between patients who had biochemical recurrence as opposed to those who did not. We further performed differential gene expression and cell type enrichment analysis to explore the host transcriptomic and cellular responses to selected microbial genera. A public dataset (GSE115414) of total RNA sequencing reads from 24 prostate tissue samples (8 benign and 16 malignant) served as the validation cohort.ResultsWe observed decreased species diversity and significant under-representation ofStaphylococcus saprophyticusandVibrio parahaemolyticus, as well as significant over-abundance ofShewanellain malignant as compared to benign prostate tissue samples in both the discovery (p< 0.01) and validation (p< 0.05) cohorts. In addition, we identifiedMicrobacteriumspecies (p< 0.01) to be significantly over-abundant in pathologically advanced T3 tumors compared to T2 in the discovery cohort. Malignant samples having high vs. lowShewanellacounts were associated with downregulated Toll-like receptor signaling pathways and decreased enrichment of dendritic cells. Malignant samples having low vs. highV. parahaemolyticuscounts were enriched for olfactory transduction and drug metabolism pathways. Finally, malignant samples were enriched for M1 and M2 macrophages as compared to benign tissue samples.ConclusionsThe results from this exploratory study support the existence of an important biological link between the prostate microbiota and PCa development/progression. Our results highlightShewanella,V. parahaemolyticus, andMicrobacterium sp.as interesting candidates for further investigation of their association with PCa.
Fifteen years of enzyme replacement therapy for mucopolysaccharidosis type VI (Maroteaux–Lamy syndrome): a case report
Authors: Andrade Isadora , Ribeiro River , Carneiro Zumira A. , Giugliani Roberto , Pereira Catarina , Cozma Claudia , Grinberg Daniel , Vilageliu Lluïsa , Lourenco Charles M. 
Published: January 2022

Abstract
Background
Mucopolysaccharidosis VI, or Maroteaux–Lamy disease, is an autosomal recessive disease characterized by deficiency of the enzyme arylsulfatase B in the lysosomal catabolism of glycosaminoglycans. Due to reduced (or even null) enzyme activity, glycosaminoglycans (mainly dermatan sulfate) accumulates, leading to a multisystemic disease. Mucopolysaccharidosis VI induces reduced growth, coarse face, audiovisual deficits, osteoarticular deformities, and cardiorespiratory issues, hampering the quality of life of the patient. Enzyme replacement therapy with galsulfase (Naglazyme, BioMarin Pharmaceuticals Inc., USA) is the specific treatment for this condition. Although studies have shown that enzyme replacement therapy slows the progression of the disease, the effects of long-term enzyme replacement therapy remain poorly understood.

Case presentation
A 29-year-old, Caucasian, male patient diagnosed with mucopolysaccharidosis VI was treated with enzyme replacement therapy for over 15 years. Enzyme replacement therapy was initiated when patient was 13 years old. The patient evolved multiplex dysostosis, carpal tunnel syndrome, thickened mitral valve, and hearing and visual loss.

Conclusions
Although enzyme replacement therapy did not prevent the main signs of mucopolysaccharidosis VI, it slowed their progression. Additionally, enzyme replacement therapy was associated with a longer survival compared with the untreated affected sibling. Taken together, the results indicate that enzyme replacement therapy positively modified the course of the disease.
Robust error estimation based on factor-graph models for non-line-of-sight localization
Authors: Vanli O. Arda , Taylor Clark N. 
Published: January 2022

AbstractThis paper presents a method to estimate the covariances of the inputs in a factor-graph formulation for localization under non-line-of-sight conditions. A general solution based on covariance estimation and M-estimators in linear regression problems, is presented that is shown to give unbiased estimators of multiple variances and are robust against outliers. An iteratively re-weighted least squares algorithm is proposed to jointly compute the proposed variance estimators and the state estimates for the nonlinear factor graph optimization. The efficacy of the method is illustrated in a simulation study using a robot localization problem under various process and measurement models and measurement outlier scenarios. A case study involving a Global Positioning System based localization in an urban environment and data containing multipath problems demonstrates the application of the proposed technique.