bluuebunny/crossref_metadata_2025_split huggingface dataset:
Catastrophic health expenditure among single empty-nest elderly with multimorbidity in rural Shandong, China: the effect of co-occurrence of frailty
Authors: Jing Zhengyue , Li Jie , Fu Pei Pei , Wang Yi , Yuan Yemin , Zhao Dan , Hao Wenting , Yu Caiting , Zhou Chengchao 
Published: January 2021

Abstract
Background
Previous studies have indicated that older adults with multimorbidity had higher risk of incurring catastrophic health expenditure (CHE). However, the effect of co-occurrence of frailty on CHE among single empty-nest elderly with multimorbidity remains unclear. This study aims to explore the effect of co-occurrence of frailty on CHE among single empty-nest elderly with multimorbidity, and whether this effect is moderated by economic status.

Methods
A cross-sectional household survey of the older adults in 2019 in Shandong province, China. A total of 606 single empty-nest elderly aged 60 years or older were included in this study. CHE was defined as the out-of-pocket payments for health care that equals or exceeds 40% of the household’ s capacity to pay. Logistic regression models are employed to examine the effect of co-occurrence of frailty on CHE among single empty-nest elderly with multimorbidity. The interaction term is introduced to explore the economic status difference in this effect.

Results
The CHE incidence for single empty-nest elderly with multimorbidity alone is 64.2%, and the co-occurrence of frailty results in an increase by almost 1.3 times (84.0%) in CHE incidence among single empty-nest elderly with multimorbidity. The co-occurrence of frailty increases the risk of incurring CHE among the single empty-nest elderly with multimorbidity, with the odds of incurring CHE increased by 3.19 times (OR = 3.19; P = 0.005). Furthermore, the interaction analysis shows that the effect of co-occurrence of frailty on CHE among single empty-nest elderly with multimorbidity still exist in lower economic status groups (OR = 4.64; P = 0.027), but not in higher economic status (OR = 2.76; P = 0.062).

Conclusions
This study demonstrates that there is a positive effect of co-occurrence of frailty on the CHE among the single empty-nest elderly with multimorbidity, and this effect varies by economic status. The health policy-makers should reorganize the healthcare system to make it pro-poor, so as to meet the multiple medical demand and reduce the potential economic burden and inequalities of older adults.
Exploring equity and inclusion in Malawi’s National Disability Mainstreaming Strategy and Implementation Plan
Authors: Ebuenyi Ikenna D. , Smith Emma M. , Munthali Alister , Msowoya Steven W. , Kafumba Juba , Jamali Monica Z. , MacLachlan Malcolm 
Published: January 2021

Abstract
Background
Equity and inclusion are important principles in policy development and implementation. The aim of this study is to explore the extent to which equity and inclusion were considered in the development of Malawi’s National Disability Mainstreaming Strategy and Implementation Plan.

Methods
We applied an analytical methodology to review the Malawi’s National Disability Mainstreaming Strategy and Implementation Plan using the EquIPP (Equity and Inclusion in Policy Processes) tool. The EquIPP tool assesses 17 Key Actions to explore the extent of equity and inclusion.

Results
The development of the Malawi National Disability Mainstreaming Strategy and Implementation Plan was informed by a desire to promote the rights, opportunities and wellbeing of persons with disability in Malawi. The majority (58%) of the Key Actions received a rating of three, indicating evidence of clear, but incomplete or only partial engagement of persons with disabilities in the policy process. Three (18%) of the Key Actions received a rating of four indicating that all reasonable steps to engage in the policy development process were observed. Four (23%) of the Key Actions received a score five indicating a reference to Key Action in the core documents in the policy development process.

Conclusions
The development of disability policies and associated implementation strategies requires equitable and inclusive processes that consider input from all stakeholders especially those whose wellbeing depend on such policies. It is pivotal for government and organisations in the process of policy or strategy development and implementation, to involve stakeholders in a virtuous process of co-production – co-implementation – co-evaluation, which may strengthen both the sense of inclusion and the effectiveness of the policy life-cycle.
Metabolomic signatures of the long-term exposure to air pollution and temperature
Authors: Nassan Feiby L. , Kelly Rachel S. , Kosheleva Anna , Koutrakis Petros , Vokonas Pantel S. , Lasky-Su Jessica A. , Schwartz Joel D. 
Published: January 2021

AbstractBackgroundLong-term exposures to air pollution has been reported to be associated with inflammation and oxidative stress. However, the underlying metabolic mechanisms remain poorly understood.ObjectivesWe aimed to determine the changes in the blood metabolome and thus the metabolic pathways associated with long-term exposure to outdoor air pollution and ambient temperature.MethodsWe quantified metabolites using mass-spectrometry based global untargeted metabolomic profiling of plasma samples among men from the Normative Aging Study (NAS). We estimated the association between long-term exposure to PM2.5, NO2, O3, and temperature (annual average of central site monitors) with metabolites and their associated metabolic pathways. We used multivariable linear mixed-effect regression models (LMEM) while simultaneously adjusting for the four exposures and potential confounding and correcting for multiple testing. As a reduction method for the intercorrelated metabolites (outcome), we further used an independent component analysis (ICA) and conducted LMEM with the same exposures.ResultsMen (N = 456) provided 648 blood samples between 2000 and 2016 in which 1158 metabolites were quantified. On average, men were 75.0 years and had an average body mass index of 27.7 kg/m2. Almost all men (97%) were not current smokers. The adjusted analysis showed statistically significant associations with several metabolites (58 metabolites with PM2.5, 15 metabolites with NO2, and 6 metabolites with temperature) while no metabolites were associated with O3. One out of five ICA factors (factor 2) was significantly associated with PM2.5. We identified eight perturbed metabolic pathways with long-term exposure to PM2.5and temperature: glycerophospholipid, sphingolipid, glutathione, beta-alanine, propanoate, and purine metabolism, biosynthesis of unsaturated fatty acids, and taurine and hypotaurine metabolism. These pathways are related to inflammation, oxidative stress, immunity, and nucleic acid damage and repair.ConclusionsUsing a global untargeted metabolomic approach, we identified several significant metabolites and metabolic pathways associated with long-term exposure to PM2.5, NO2and temperature. This study is the largest metabolomics study of long-term air pollution, to date, the first study to report a metabolomic signature of long-term temperature exposure, and the first to use ICA in the analysis of both.
Development of targeted therapy therapeutics to sensitize triple-negative breast cancer chemosensitivity utilizing bacteriophage phi29 derived packaging RNA
Authors: Zhang Long , Mu Chaofeng , Zhang Tinghong , Yang Dejun , Wang Chenou , Chen Qiong , Tang Lin , Fan Luhui , Liu Cong , Shen Jianliang , Li Huaqiong 
Published: January 2021

Abstract
Background
To date, triple-negative breast cancer (TNBC) treatment options are limited because of the loss of target receptors and, as a result, are only managed with chemotherapy. What is worse is that TNBC is frequently developing resistance to chemotherapy. By using small interfering RNA (siRNA)-based therapeutics, our recent work demonstrated X-box-binding protein 1 (XBP1) was linked to human epidermal growth factor receptor 2 positive (HER2+) breast cancer development and chemoresistance. Given the instability, off-target effects, net negative charge, and hydrophobicity of siRNA in vivo utilization and clinical transformation, its use in treatment is hampered. Thus, the development of a siRNA-based drug delivery system (DDS) with ultra-stability and specificity is necessary to address the predicament of siRNA delivery.

Results
Here, we assembled RNase resistant RNA nanoparticles (NPs) based on the 3WJ structure from Phi29 DNA packaging motor. To improved targeted therapy and sensitize TNBC to chemotherapy, the RNA NPs were equipped with an epidermal growth factor receptor (EGFR) targeting aptamer and XBP1 siRNA. We found our RNA NPs could deplete XBP1 expression and suppress tumor growth after intravenous administration. Meanwhile, RNA NPs treatment could promote sensitization to chemotherapy and impede angiogenesis in vivo.

Conclusions
The results further demonstrate that our RNA NPs could serve as an effective and promising platform not only for siRNA delivery but also for chemotherapy-resistant TNBC therapy.
FSH regulates RA signaling to commit spermatogonia into differentiation pathway and meiosis
Authors: Khanehzad Maryam , Abbaszadeh Roya , Holakuyee Marzieh , Modarressi Mohammad Hossein , Nourashrafeddin Seyed Mehdi 
Published: January 2021

AbstractBackgroundSpermatogenesis is a complex process that is controlled by interactions between germ cells and somatic cells. The commitment of undifferentiated spermatogonia to differentiating spermatogonia and normal spermatogenesis requires the action of gonadotropins. Additionally, numerous studies revealed the role of retinoic acid signaling in induction of germ cell differentiation and meiosis entry.Main textRecent studies have shown that expression of several RA signaling molecules including Rdh10, Aldh1a2, Crabp1/2 are influenced by changes in gonadotropin levels. Components of signaling pathways that are regulated by FSH signaling such as GDNF, Sohlh1/2, c-Kit, DMRT, BMP4 and NRGs along with transcription factors that are important for proliferation and differentiation of spermatogonia are also affected by retinoic acid signaling.ConclusionAccording to all studies that demonstrate the interface between FSH and RA signaling, we suggest that RA may trigger spermatogonia differentiation and initiation of meiosis through regulation by FSH signaling in testis. Therefore, to the best of our knowledge, this is the first time that the correlation between FSH and RA signaling in spermatogenesis is highlighted.
Designing provider-focused implementation trials with purpose and intent: introducing the PRECIS-2-PS tool
Authors: Norton Wynne E. , Loudon Kirsty , Chambers David A. , Zwarenstein Merrick 
Published: January 2021

Abstract
Background
First articulated by Schwartz and Lellouch (1967), randomized controlled trials (RCTs) can be conceptualized along a continuum from more explanatory to more pragmatic. The purpose and intent of the former is to test interventions under ideal contexts, and the purpose and intent of the latter is to test interventions in real-world contexts. The PRagmatic Explanatory Continuum Indicator Summary-2 (PRECIS-2) is a validated tool that helps researchers make decisions about the elements of the trial to match the overall purpose and intent of the trial along the continuum. The PRECIS-2 tool has guided the design of hundreds of RCTs. However, a few aspects of the tool would benefit from greater clarity, including its application to provider-focused implementation trials rather than patient-focused intervention trials.

Main text
We describe the newly developed PRECIS-2-Provider Strategies (PRECIS-2-PS) tool, an extension of the PRECIS-2 tool, which has been adapted for trials testing provider-focused strategies. We elaborate on nine domains that can make a provider-focused trial more explanatory or more pragmatic, including eligibility, recruitment, setting, implementation resources, flexibility of provider strategies, flexibility of intervention, data collection, primary outcome, and primary analysis. We detail the complementary roles that researchers and stakeholders play in the trial design phase, with implications for generalizability of trial results to the contexts in which they are intended to be applied.

Conclusions
The PRECIS-2-PS tool is designed to help research and practice teams plan for provider-focused trials that reflect the overall intent and purpose of the trial. The tool has potential to help advance the science of provider-focused strategies across a range of trials, with the ultimate goal of facilitating the adoption, integration, and sustainability of provider-focused strategies outside the context of trials.
Exosomal miR-186 derived from BMSCs promote osteogenesis through hippo signaling pathway in postmenopausal osteoporosis
Authors: Li Lu , Zhou Xin , Zhang Jun-tao , Liu Ai-feng , Zhang Chao , Han Jin-chang , Zhang Xiao-qing , Wu Si , Zhang Xiao-yu , Lv Fu-quan 
Published: January 2021

Abstract
Background
Postmenopausal osteoporosis (PMO) that results from estrogen withdrawal is the most common primary osteoporosis among older women. However, little is known about the mechanism of PMO, and effective treatment of PMO is limited.

Methods
We used real-time polymerase chain reaction (qPCR), Western blotting, and RNA pull down to investigate the relationship between miR-186 and MOB Kinase Activator 1A (Mob1). Also, we investigated the effect of exosome in osteogenesis using alkaline phosphatase (ALP) staining. And hematoxylin eosin (HE) staining was used to verify the osteogenesis in PMO model.

Results
Exosomal miR-186 plays an important role in bone formation. The results of miRNA-seq and q-PCR showed that miR-186 was upregulated in a PMO + Exo treatment group. Results of RNA-pull down and luciferase reporter assays verified interactions between miR-186 and Mob1. We also verified the Hippo signaling pathway plays an important role in osteogenesis.

Conclusions
We concluded that exosomes derived from human bone marrow mesenchymal stem cells (hBMSCs) can transfer miR-186 to promote osteogenesis in ovariectomy (OVX) rats through the Hippo signaling pathway.
Hemodynamic and anti-inflammatory effects of early esmolol use in hyperkinetic septic shock: a pilot study
Authors: Levy Bruno , Fritz Caroline , Piona Caroline , Duarte Kevin , Morelli Andrea , Guerci Philippe , Kimmoun Antoine , Girerd Nicolas 
Published: January 2021

Abstract
Background
Several studies have shown that heart rate control with selective beta-1 blockers in septic shock is safe. In these trials, esmolol was administered 24 h after onset of septic shock in patients who remained tachycardic. While an earlier use of beta-blockers might be beneficial, such use remains challenging due to the difficulty in distinguishing between compensatory and non-compensatory tachycardia. Therefore, the Esmosepsis study was designed to study the effects of esmolol aimed at reducing the heart rate by 20% after the initial resuscitation process in hyperkinetic septic shock patients on (1) cardiac index and (2) systemic and regional hemodynamics as well as inflammatory patterns.

Methods
Nine consecutive stabilized tachycardic hyperkinetic septic shock patients treated with norepinephrine for a minimum of 6 h were included. Esmolol was infused during 6 h in order to decrease the heart rate by 20%. The following data were recorded at hours H0 (before esmolol administration), H1–H6 (esmolol administration) and 1 h after esmolol cessation (H7): systolic arterial pressure, diastolic arterial pressure, mean arterial pressure, central venous pressure, heart rate, PICCO transpulmonary thermodilution, sublingual and musculo-cutaneous microcirculation, indocyanine green clearance and echocardiographic parameters, diuresis, lactate, and arterial and venous blood gases.

Results
Esmolol was infused 9 (6.4–11.6) hours after norepinephrine introduction. Esmolol was ceased early in 3 out of 9 patients due to a marked increase in norepinephrine requirement associated with a picture of persistent cardiac failure at the lowest esmolol dose. For the global group, during esmolol infusion, norepinephrine infusion increased from 0.49 (0.34–0.83) to 0.78 (0.3–1.11) µg/min/kg. The use of esmolol was associated with a significant decrease in heart rate from 115 (110–125) to 100 (92–103) beats/min and a decrease in cardiac index from 4.2 (3.1–4.4) to 2.9 (2.5–3.7) l/min/m−2. Indexed stroke volume remained unchanged. Cardiac function index and global ejection fraction also markedly decreased. Using echocardiography, systolic, diastolic as well as left and right ventricular function parameters worsened. After esmolol cessation, all parameters returned to baseline values. Lactate and microcirculatory parameters did not change while the majority of pro-inflammatory proteins decreased in all patients.

Conclusion
In the very early phase of septic shock, heart rate reduction using fast esmolol titration is associated with an increased risk of hypotension and decreased cardiac index despite maintained adequate tissue perfusion (NCT02068287).
NRG1 fusions in breast cancer
Authors: Howarth Karen D. , Mirza Tashfina , Cooke Susanna L. , Chin Suet-Feung , Pole Jessica C. , Turro Ernest , Eldridge Matthew D. , Garcia Raquel Manzano , Rueda Oscar M. , Boursnell Chris , Abraham Jean E. , Caldas Carlos , Edwards Paul A. W. 
Published: January 2021

AbstractBackgroundNRG1gene fusions may be clinically actionable, since cancers carrying the fusion transcripts can be sensitive to tyrosine kinase inhibitors. TheNRG1gene encodes ligands for the HER2(ERBB2)-ERBB3 heterodimeric receptor tyrosine kinase, and the gene fusions are thought to lead to autocrine stimulation of the receptor. TheNRG1fusion expressed in the breast cancer cell line MDA-MB-175 serves as a model example of such fusions, showing the proposed autocrine loop and exceptional drug sensitivity. However, its structure has not been properly characterised, its oncogenic activity has not been fully explained, and there is limited data on such fusions in breast cancer.MethodsWe analysed genomic rearrangements and transcripts ofNRG1in MDA-MB-175 and a panel of 571 breast cancers.ResultsWe found that the MDA-MB-175 fusion—originally reported as aDOC4(TENM4)-NRG1fusion, lacking the cytoplasmic tail ofNRG1—is in reality a double fusion,PPP6R3-TENM4-NRG1, producing multiple transcripts, some of which include the cytoplasmic tail. We hypothesise that manyNRG1fusions may be oncogenic not for lacking the cytoplasmic domain but because they do not encode NRG1’s nuclear-localised form. The fusion in MDA-MB-175 is the result of a very complex genomic rearrangement, which we partially characterised, that creates additional expressed gene fusions,RSF1-TENM4,TPCN2-RSF1, andMRPL48-GAB2.We searched forNRG1rearrangements in 571 breast cancers subjected to genome sequencing and transcriptome sequencing and found four cases (0.7%) with fusions,WRN-NRG1,FAM91A1-NRG1,ARHGEF39-NRG1, andZNF704-NRG1, all splicing intoNRG1at the same exon as in MDA-MB-175. However, theWRN-NRG1andARHGEF39-NRG1fusions were out of frame. We identified rearrangements ofNRG1in many more (8% of) cases that seemed more likely to inactivate than to create activating fusions, or whose outcome could not be predicted because they were complex, or both. This is not surprising becauseNRG1can be pro-apoptotic and isinactivated in some breast cancers.ConclusionsOur results highlight the complexity of rearrangements ofNRG1in breast cancers and confirm that some do not activate but inactivate. Careful interpretation ofNRG1rearrangements will therefore be necessary for appropriate patient management.
Description of a rat model of polymicrobial abdominal sepsis mimicking human colon perforation
Authors: Utiger Julia M. , Glas Michael , Levis Anja , Prazak Josef , Haenggi Matthias 
Published: January 2021

Abstract
Objective
Standard rodent sepsis models as cecal ligation and puncture models (CLP) or cecal ligation and incision models (CLI) are frequently not suited experiments, mainly because they lack surgical repair, and they are difficult to control for severity. The colon ascendens stent peritonitis model (CASP) overcomes some of these limitations.

Result
Here we present our modification of the rodent CASP model, where severity of sepsis can be controlled by timing of surgical repair and treatment, and by diameter of the stent. Further, basic hemodynamic monitoring (blood pressure and heart rate) and frequent blood sampling can be achieved, which might guide further treatment.
Biochemical and molecular changes of the zosteric acid-treated Escherichia coli biofilm on a mineral surface
Authors: Villa Federica , Secundo Francesco , Forlani Fabio , Cattò Cristina , Cappitelli Francesca 
Published: January 2021

Abstract
Purpose
The main goal of the present work was to assess the effectiveness of zosteric acid (ZA) in hindering Escherichia coli biofilm formation on a mineral surface.

Methods
Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) flow system was used to probe in situ the biochemical changes induced by ZA on E. coli sessile cells growing on the zinc selenide ATR plate. Comparative proteome analysis was conducted on the sessile cells to better understand the principal molecular changes that occur on ZA-treated biofilms.

Results
The ZA treatment modified the kinetics of the biofilm development. After the ZA exposure, dramatic changes in the carbohydrates, proteins, and DNA profiles were observed over time in the ATR-FTIR spectra. These results were translated into the physiological effects such as the reduction of both the biomass and the EPS contents, the inhibition of the biofilm growth, and the promotion of the detachment. In E. coli sessile cells, the comparative proteome analysis revealed that, while the stress responses were upregulated, the pathways belonging to the DNA replication and repair were downregulated in the ZA-treated biofilms.

Conclusions
The ZA reduced the binding capability of E. coli cells onto the ZnSe crystal, hindering the firm adhesion and the subsequent biofilm development on a mineral surface. The variation of the protein patterns indicated that the ZA acted as a stress factor on the sessile cells that seemed to discourage biomass proliferation, consequently decreasing the surface colonization.