bluuebunny/crossref_metadata_2025_split huggingface dataset:
Covid-19 and pathways to health inequities for families in a socioeconomically disadvantaged area of Sweden – qualitative analysis of home visitors’ observations
Authors: Barboza Madelene , Marttila Anneli , Burström Bo , Kulane Asli 
Published: September 2021

AbstractBackgroundLack of control over life situations is an important social determinant that may negatively affect parental and child health. This study took place in an area of Stockholm, Sweden with high indications of socioeconomic disadvantage, a large part of the population with foreign background, as well as higher levels of poor health than the county average. It investigated staff perceptions of pathways from situations of low control, potentially leading to health inequities, affecting families enrolled in an early childhood home visiting programme during the Covid-19 pandemic.MethodsSemi-structured interviews were carried out with 23 child health care nurses and parental advisors working in a home visiting programme. The data was analysed using Reflexive Thematic Analysis.ResultsThe analysis resulted in five pathways on two explanatory levels, affecting parents’ health and parenting capacity and children’s health and well-being, potentially damaging health and leading to health inequities. The first four pathways related to control at the personal explanatory level: Families facing instability and insecurity; Caring for children in crowded and poor housing conditions; Experiencing restricted access to resources; and Parenting with limited social support. The fifth pathway, Living in a segregated society, covered the collective experience of lack of control on community level. The Covid-19 pandemic was observed to negatively affect all pathways and thus potentially aggravate health inequities for this population. The pandemic has also limited the delivery of home visits to the families which creates further barriers in families’ access to resources and increases isolation for parents with already limited social support.ConclusionsThe diversity of pathways connected to health inequities presented in this study highlights the importance of considering this variety of influences when designing interventions for socioeconomically disadvantaged areas. The additional negative consequences of Covid-19 indicate the need for sustainable preventive early childhood interventions for families in such areas. The study also emphasizes the need for further research as well as policy action on possible long-term effects of changing behaviours during the Covid-19 period on child health and health equity.Trial registrationThe study was retrospectively registered (11 August 2016) in the ISRCTN registry (ISRCTN11832097).
Increased expression level of ANGPTL8 in white adipose tissue under acute and chronic cold treatment
Authors: Arefanian Hossein , Al-Khairi Irina , Khalaf Nermeen Abu , Cherian Preethi , Kavalakatt Sina , Madhu Dhanya , Mathur Aditi , Qaddoumi Mohamed G. , Al-Mulla Fahd , Abubaker Jehad , Abu-Farha Mohamed 
Published: September 2021

Abstract
Background
Angiopoietin-like proteins (ANGPTL), primarily 3, 4, and 8, play a major role in maintaining energy homeostasis by regulating triglyceride metabolism. This study evaluated the level of ANGPTL3, 4, and 8 in the liver, brown adipose tissue (BAT), and subcutaneous white adipose tissue (SAT) of mice maintained under acute and chronic cold conditions.

Methods
C57BL/6J mice were exposed to cold temperature (4 °C) for 10 days with food provided ad libitum. Animal tissues were harvested at Day 0 (Control group, n = 5) and Days 1, 3, 5, and 10 (cold treatment groups, n = 10 per group). The expression levels of various genes were measured in the liver, SAT, and BAT. ANGPTL3, 4, and 8 expressions were measured in the liver. ANGPTL4, 8, and genes involved in browning and lipid metabolism [uncoupling protein 1 (UCP1), lipoprotein lipase (LPL), and adipose triglyceride lipase (ATGL)] were measured in SAT and BAT. Western blotting (WB) analysis and immunohistochemistry (IHC) were performed to confirm ANGPTL8 expression in these tissues.

Results
The expressions of ANGPTL3 and 8 mRNA were significantly reduced in mouse liver tissues after cold treatment (P < 0.05); however, the expression of ANGPTL4 was not significantly altered. In BAT, ANGPTL8 expression was unchanged after cold treatment, whereas ANGPTL4 expression was significantly reduced (P < 0.05). ANGPTL4 levels were also significantly reduced in SAT, whereas ANGPTL8 gene expression exhibited over a 5-fold increase. Similarly, UCP1 gene expression was also significantly increased in SAT. The mRNA levels of LPL and ATGL showed an initial increase followed by a gradual decrease with an increase in the days of cold exposure. ANGPTL8 protein overexpression was further confirmed by WB and IHC.

Conclusions
This study shows that exposure to acute and chronic cold treatment results in the differential expression of ANGPTL proteins in the liver and adipose tissues (SAT and BAT). The results show a significant reduction in ANGPTL4 in BAT, which is linked to improved thermogenesis in response to acute cold exposure. ANGPTL8 was activated under acute and chronic cold conditions in SAT, suggesting that it is involved in regulating lipolysis and enhancing SAT browning.
Highly sensitive and portable mRNA detection platform for early cancer detection
Authors: Li Hongxia , Warden Antony R. , Su Wenqiong , He Jie , Zhi Xiao , Wang Kan , Zhu Laikuan , Shen Guangxia , Ding Xianting 
Published: September 2021

AbstractPancreatic cancer, at unresectable advanced stages, presents poor prognoses, which could be prevented by early pancreatic cancer diagnosis methods. Recently, a promising early-stage pancreatic cancer biomarker, extracellular vesicles (EVs) related glypican-1 (GPC1) mRNA, is found to overexpress in pancreatic cancer cells. Current mRNA detection methods usually require expensive machinery, strict preservation environments, and time-consuming processes to guarantee detection sensitivity, specificity, and stability. Herein, we propose a novel two-step amplification method (CHAGE) via the target triggered Catalytic Hairpin Assembly strategy combined with Gold-Enhanced point-of-care-testing (POCT) technology for sensitive visual detection of pancreatic cancer biomarker. First, utilizing the catalyzed hairpin DNA circuit, low expression of the GPC1 mRNA was changed into amplification product 1 (AP1, a DNA duplex) as the next detection targets of the paper strips. Second, the AP1 was loaded onto a lateral flow assay and captured with the gold signal nanoparticles to visualize results. Finally, the detected results can be further enhanced by depositing gold to re-enlarge the sizes of gold nanoparticles in detection zones. As a result, the CHAGE methodology lowers the detection limit of mRNA to 100 fM and provides results within 2 h at 37 °C. Furthermore, we demonstrate the successful application in discriminating pancreatic cancer cells by analyzing EVs’ GPC1 mRNA expression levels. Hence, the CHAGE methodology proposed here provides a rapid and convenient POCT platform for sensitive detection of mRNAs through unique probes designs (COVID, HPV, etc.).
Endogenous microRNA triggered enzyme-free DNA logic self-assembly for amplified bioimaging and enhanced gene therapy via in situ generation of siRNAs
Authors: Jiang Qinghua , Yue Shuzhen , Yu Kaixin , Tian Tian , Zhang Jian , Chu Huijun , Cui Zhumei , Bi Sai 
Published: September 2021

Abstract
Background
Small interfering RNA (siRNA) has emerged as a kind of promising therapeutic agents for cancer therapy. However, the off-target effect and degradation are the main challenges for siRNAs delivery. Herein, an enzyme-free DNA amplification strategy initiated by a specific endogenous microRNA has been developed for in situ generation of siRNAs with enhanced gene therapy effect on cervical carcinoma.

Methods
This strategy contains three DNA hairpins (H1, H2/PS and H3) which can be triggered by microRNA-21 (miR-21) for self-assembly of DNA nanowheels (DNWs). Notably, this system is consistent with the operation of a DNA logic circuitry containing cascaded “AND” gates with feedback mechanism. Accordingly, a versatile biosensing and bioimaging platform is fabricated for sensitive and specific analysis of miR-21 in HeLa cells via fluorescence resonance energy transfer (FRET). Meanwhile, since the vascular endothelial growth factor (VEGF) antisense and sense sequences are encoded in hairpin reactants, the performance of this DNA circuit leads to in situ assembly of VEGF siRNAs in DNWs, which can be specifically recognized and cleaved by Dicer for gene therapy of cervical carcinoma.

Results
The proposed isothermal amplification approach exhibits high sensitivity for miR-21 with a detection limit of 0.25 pM and indicates excellent specificity to discriminate target miR-21 from the single-base mismatched sequence. Furthermore, this strategy achieves accurate and sensitive imaging analysis of the expression and distribution of miR-21 in different living cells. To note, compared to naked siRNAs alone, in situ siRNA generation shows a significantly enhanced gene silencing and anti-tumor effect due to the high reaction efficiency of DNA circuit and improved delivery stability of siRNAs.

Conclusions
The endogenous miRNA-activated DNA circuit provides an exciting opportunity to construct a general nanoplatform for precise cancer diagnosis and efficient gene therapy, which has an important significance in clinical translation.

Graphic abstract
Development of a competitive chemiluminescence immunoassay using a monoclonal antibody recognizing 3B of foot-and-mouth disease virus for the rapid detection of antibodies induced by FMDV infection
Authors: Liu Wei , Zhang Guanglei , Yang Sicheng , Li Junhui , Gao Zhan , Ge Sudan , Yang Huihui , Shao Junjun , Chang Huiyun 
Published: September 2021

Abstract
Background
Foot-and-mouth disease (FMD) is a devastating animal disease. Anti-non-structural protein (NSP) antibody detection is very important for confirming suspected cases, evaluating the prevalence of infection, certifying animals for trade and controlling the disease.

Methods
In this study, a competitive chemiluminescence immunoassay (3B-cCLIA) was developed for the rapid detection of antibodies against NSPs in different species of livestock animals using the monoclonal antibody (mAb) 9E2 as a competitive antibody that recognizes NSP 3B.

Results
The cut-off value (50%), diagnostic sensitivity (Dsn) (97.20%, 95.71%, and 96.15%) and diagnostic specificity (Dsp) (99.51%, 99.43%, and 98.36) of the assay were estimated by testing a panel of known-background sera from swine, cattle and sheep, respectively. The accuracy rate of the 3B-cCLIA was further validated and subsequently compared with that of two commercial diagnostic kits. The early diagnostic results showed that antibodies recognizing NSPs developed later (approximately 1–2 days) than antibodies recognizing structural proteins. Furthermore, anti-NSP antibody presence in animals vaccinated multiple times (false positives), especially cattle and sheep, was confirmed, and the false-positive rate increased with the number of vaccinations.

Conclusions
These results indicate that the 3B-cCLIA is suitable for the rapid detection of antibodies against FMDV NSP 3B in a wide range of species.
Regulation of plant antiviral defense genes via host RNA-silencing mechanisms
Authors: Leonetti Paola , Stuttmann Johannes , Pantaleo Vitantonio 
Published: September 2021

Abstract
Background
Plants in nature or crops in the field interact with a multitude of beneficial or parasitic organisms, including bacteria, fungi and viruses. Viruses are highly specialized to infect a limited range of host plants, leading in extreme cases to the full invasion of the host and a diseased phenotype. Resistance to viruses can be mediated by various passive or active mechanisms, including the RNA-silencing machinery and the innate immune system.

Main text
RNA-silencing mechanisms may inhibit viral replication, while viral components can elicit the innate immune system. Viruses that successfully enter the plant cell can elicit pattern-triggered immunity (PTI), albeit by yet unknown mechanisms. As a counter defense, viruses suppress PTI. Furthermore, viral Avirulence proteins (Avr) may be detected by intracellular immune receptors (Resistance proteins) to elicit effector-triggered immunity (ETI). ETI often culminates in a localized programmed cell death reaction, the hypersensitive response (HR), and is accompanied by a potent systemic defense response. In a dichotomous view, RNA silencing and innate immunity are seen as two separate mechanisms of resistance. Here, we review the intricate connections and similarities between these two regulatory systems, which are collectively required to ensure plant fitness and resilience.

Conclusions
The detailed understanding of immune regulation at the transcriptional level provides novel opportunities for enhancing plant resistance to viruses by RNA-based technologies. However, extensive use of RNA technologies requires a thorough understanding of the molecular mechanisms of RNA gene regulation. We describe the main examples of host RNA-mediated regulation of virus resistance.
Surface charge-dependent mitochondrial response to similar intracellular nanoparticle contents at sublethal dosages
Authors: Jin Xiaoting , Yu Haiyi , Zhang Ze , Cui Tenglong , Wu Qi , Liu Xiaolei , Gao Jie , Zhao Xingchen , Shi Jianbo , Qu Guangbo , Jiang Guibin 
Published: September 2021

Abstract
Background
Considering the inevitability for humans to be frequently exposed to nanoparticles (NPs), understanding the biosafety of NPs is important for rational usage. As an important part of the innate immune system, macrophages are widely distributed in vital tissues and are also a dominant cell type that engulfs particles. Mitochondria are one of the most sensitive organelles when macrophages are exposed to NPs. However, previous studies have mainly reported the mitochondrial response upon high-dose NP treatment. Herein, with gold nanoparticles (AuNPs) as a model, we investigated the mitochondrial alterations induced by NPs at a sublethal concentration.

Results
At a similar internal exposure dose, different AuNPs showed distinct degrees of effects on mitochondrial alterations, including reduced tubular mitochondria, damaged mitochondria, increased reactive oxygen species, and decreased adenosine triphosphate. Cluster analysis, two-way ANOVA, and multiple linear regression suggested that the surface properties of AuNPs were the dominant determinants of the mitochondrial response. Based on the correlation analysis, the mitochondrial response was increased with the change in zeta potential from negative to positive. The alterations in mitochondrial respiratory chain proteins indicated that complex V was an indicator of the mitochondrial response to low-dose NPs.

Conclusion
Our current study suggests potential hazards of modified AuNPs on mitochondria even under sublethal dose, indicates the possibility of surface modification in biocompatibility improvement, and provides a new way to better evaluation of nanomaterials biosafety.
Familiar but neglected: identification of gaps and recommendations to close them on exclusive breastfeeding support in health facilities in Malawi
Authors: Nyondo-Mipando Alinane Linda , Kinshella Mai-Lei Woo , Salimu Sangwani , Chiwaya Brandina , Chikoti Felix , Chirambo Lusungu , Mwaungulu Ephrida , Banda Mwai , Newberry Laura , Hiwa Tamanda , Vidler Marianne , Dube Queen , Molyneux Elizabeth , Mfutso-Bengo Joseph , Goldfarb David M. , Kawaza Kondwani 
Published: September 2021

Abstract
Background
Exclusive breastfeeding is widely accepted as a key intervention with proven efficacy for improving newborn survival. Despite international commitments and targets to support and promote breastfeeding, there are still gaps in meeting and maintain coverage in many sub-Saharan African countries. This paper aimed to triangulate the perspectives of health workers, mothers, and their family members with facility assessments to identify gaps to improve breastfeeding support in in Malawi.

Methods
The study on breastfeeding barriers and facilitators was conducted in 2019 at one tertiary hospital and three secondary-level hospitals in Malawi. We conducted 61 semi-structured interviews with health workers, postnatal mothers, grandmothers, aunts, and fathers. In 2017, we carried out a neonatal care facility assessment using the World Health Organization (WHO) Integrated Maternal, Neonatal, and Child Quality of Care Assessment and Improvement Tool. Qualitative data were analysed using a thematic analysis approach within the Systems Framework for Health Policy.

Results
The district-level hospitals rated high with an average score of 4.8 out of 5 across the three facilities indicating that only minor improvements are needed to meet standards of care for early and exclusive breastfeeding. However, the score fell to an average of 3.5 out of 5 for feeding needs with sick neonates indicating that several improvements are needed in this area. The qualitative data demonstrated that breastfeeding was normalized as part of routine newborn care. However, the focus on routine practice and reliance on breastfeeding knowledge from prenatal counselling highlights inequities and neglect in specialized care and counselling among vulnerable mothers and newborns. Revitalisation of breastfeeding in Malawian facilities will require a systems approach that reinforces policies and guidelines; contextualises knowledge; engagement and empowerment of other relatives to the baby and task-sharing among health workers.

Conclusions
Breastfeeding is accepted as a social norm among health workers, mothers, grandmothers, aunts, and fathers in Malawi, yet vulnerable groups are underserved. Neglect in breastfeeding support among vulnerable populations exacerbates health inequities. Health systems strengthening related to breastfeeding requires a concerted effort among health workers, mothers, grandmothers, aunts, and fathers while remaining grounded in contexts to support family-centered hospital care.
Socioeconomic correlates of incident and fatal opioid overdose among Swedish people with opioid use disorder
Authors: Dahlman Disa , Ohlsson Henrik , Edwards Alexis C. , Sundquist Jan , Håkansson Anders , Sundquist Kristina 
Published: September 2021

Abstract
Background
Opioid overdose (OD) and opioid OD death are major health threats to people with opioid use disorder (OUD). Socioeconomic factors are underexplored potential determinants of opioid OD. In this study, we assessed socioeconomic and other factors and their associations with incident and fatal opioid OD, in a cohort consisting of 22,079 individuals with OUD.

Methods
We performed a retrospective, longitudinal study based on Swedish national register data for the period January 2005–December 2017. We used Cox proportional hazard models to investigate the risk of incident and fatal opioid OD as a function of several individual, parental and neighborhood covariates.

Results
Univariate analysis showed that several covariates were associated with incident and fatal opioid OD. In the multivariate analysis, incident opioid OD was associated with educational attainment (Hazard ratio [HR] 0.96; 95% confidence interval [CI] 0.94–0.97), having received social welfare (HR 1.31; 95% CI 1.22–1.39), and criminal conviction (HR 1.53; 95% CI 1.42–1.65). Fatal opioid OD was also associated with criminal conviction (HR 1.93; 95% CI 1.61–2.32).

Conclusion
Individuals with low education and receipt of social welfare had higher risks of incident opioid OD and individuals with criminal conviction were identified as a risk group for both incident and fatal opioid OD. Our findings should raise attention among health prevention policy makers in general, and among decision-makers within the criminal justice system and social services in particular.
Evaluating differences in respiratory motion estimates during radiotherapy: a single planning 4DMRI versus daily 4DMRI
Authors: den Boer Duncan , Veldman Johannes K. , van Tienhoven Geertjan , Bel Arjan , van Kesteren Zdenko 
Published: September 2021

Abstract
Background
In radiotherapy, respiratory-induced tumor motion is typically measured using a single four-dimensional computed tomography acquisition (4DCT). Irregular breathing leads to inaccurate motion estimates, potentially resulting in undertreatment of the tumor and unnecessary dose to healthy tissue. The aim of the research was to determine if a daily pre-treatment 4DMRI-strategy led to a significantly improved motion estimate compared to single planning 4DMRI (with or without outlier rejection).

Methods
4DMRI data sets from 10 healthy volunteers were acquired. The first acquisition simulated a planning MRI, the respiratory motion estimate (constructed from the respiratory signal, i.e. the 1D navigator) was compared to the respiratory signal in the subsequent scans (simulating 5–29 treatment fractions). The same procedure was performed using the first acquisition of each day as an estimate for the subsequent acquisitions that day (2 per day, 4–20 per volunteer), simulating a daily MRI strategy. This was done for three outlier strategies: no outlier rejection (NoOR); excluding 5% of the respiratory signal whilst minimizing the range (Min95) and excluding the datapoints outside the mean end-inhalation and end-exhalation positions (MeanIE).

Results
The planning MRI median motion estimates were 27 mm for NoOR, 18 mm for Min95, and 13 mm for MeanIE. The daily MRI median motion estimates were 29 mm for NoOR, 19 mm for Min95 and 15 mm for MeanIE. The percentage of time outside the motion estimate were for the planning MRI: 2%, 10% and 32% for NoOR, Min95 and MeanIE respectively. These values were reduced with the daily MRI strategy: 0%, 6% and 17%. Applying Min95 accounted for a 30% decrease in motion estimate compared to NoOR.

Conclusion
A daily MRI improved the estimation of respiratory motion as compared to a single 4D (planning) MRI significantly. Combining the Min95 technique with a daily 4DMRI resulted in a decrease of inclusion time of 6% with a 30% decrease of motion. Outlier rejection alone on a planning MRI often led to underestimation of the movement and could potentially lead to an underdosage.
Trial registration: protocol W15_373#16.007