bluuebunny/crossref_metadata_2025_split huggingface dataset:
A nuclear function for an oncogenic microRNA as a modulator of snRNA and splicing
Authors: El Fatimy Rachid , Zhang Yanhong , Deforzh Evgeny , Ramadas Mahalakshmi , Saravanan Harini , Wei Zhiyun , Rabinovsky Rosalia , Teplyuk Nadiya M. , Uhlmann Erik J. , Krichevsky Anna M. 
Published: January 2022

Abstract
Background
miRNAs are regulatory transcripts established as repressors of mRNA stability and translation that have been functionally implicated in carcinogenesis. miR-10b is one of the key onco-miRs associated with multiple forms of cancer. Malignant gliomas exhibit particularly striking dependence on miR-10b. However, despite the therapeutic potential of miR-10b targeting, this miRNA’s poorly investigated and largely unconventional properties hamper the clinical translation.

Methods
We utilized Covalent Ligation of Endogenous Argonaute-bound RNAs and their high-throughput RNA sequencing to identify miR-10b interactome and a combination of biochemical and imaging approaches for target validation. They included Crosslinking and RNA immunoprecipitation with spliceosomal proteins, a combination of miRNA FISH with protein immunofluorescence in glioma cells and patient-derived tumors, native Northern blotting, and the transcriptome-wide analysis of alternative splicing.

Results
We demonstrate that miR-10b binds to U6 snRNA, a core component of the spliceosomal machinery. We provide evidence of the direct binding between miR-10b and U6, in situ imaging of miR-10b and U6 co-localization in glioma cells and tumors, and biochemical co-isolation of miR-10b with the components of the spliceosome. We further demonstrate that miR-10b modulates U6 N-6-adenosine methylation and pseudouridylation, U6 binding to splicing factors SART3 and PRPF8, and regulates U6 stability, conformation, and levels. These effects on U6 result in global splicing alterations, exemplified by the altered ratio of the isoforms of a small GTPase CDC42, reduced overall CDC42 levels, and downstream CDC42 -mediated effects on cell viability.

Conclusions
We identified U6 snRNA, the key RNA component of the spliceosome, as the top miR-10b target in glioblastoma. We, therefore, present an unexpected intersection of the miRNA and splicing machineries and a new nuclear function for a major cancer-associated miRNA.
Augmented EPR effect post IRFA to enhance the therapeutic efficacy of arsenic loaded ZIF-8 nanoparticles on residual HCC progression
Authors: Chen Xuehua , Huang Yongquan , Chen Hui , Chen Ziman , Chen Jiaxin , Wang Hao , Li Dan , Su Zhongzhen 
Published: January 2022

Abstract
Background
Insufficient radiofrequency ablation (IRFA) can promote the local recurrence and distal metastasis of residual hepatocellular carcinoma (HCC), which makes clinical treatment extremely challenging. In this study, the malignant transition of residual tumors after IRFA was explored. Then, arsenic-loaded zeolitic imidazolate framework-8 nanoparticles (As@ZIF-8 NPs) were constructed, and their therapeutic effect on residual tumors was studied.

Results
Our data showed that IRFA can dramatically promote the proliferation, induce the metastasis, activate the epithelial–mesenchymal transition (EMT) and accelerate the angiogenesis of residual tumors. Interestingly, we found, for the first time, that extensive angiogenesis after IRFA can augment the enhanced permeability and retention (EPR) effect and enhance the enrichment of ZIF-8 nanocarriers in residual tumors. Encouraged by this unique finding, we successfully prepared As@ZIF-8 NPs with good biocompatibility and confirmed that they were more effective than free arsenic trioxide (ATO) in sublethal heat-induced cell proliferation suppression, apoptosis induction, cell migration and invasion inhibition, and EMT reversal in vitro. Furthermore, compared with free ATO, As@ZIF-8 NPs exhibited remarkably increased therapeutic effects by repressing residual tumor growth and metastasis in vivo.

Conclusions
This work provides a new paradigm for the treatment of residual HCC after IRFA.

Graphical Abstract
Health-related quality of life among Ebola survivors in Sierra Leone: the role of socio-demographic, health-related and psycho-social factors
Authors: James Peter Bai , Wardle Jon , Gyasi Razak M. , Steel Amie , Adams Jon , Kabba John Alimamy , Bah Abdulai Jawo , Lahai Michael , Conteh Eugene B. 
Published: January 2022

Abstract
Background
Evidence of how social factors affect the health-related quality of life (HRQoL) of Ebola virus disease (EVD) survivors is limited. Our study explores the association between socio-demographic, health-related and psycho-social (stigma) factors and EVD survivors' health-related quality of life (HRQoL) in Sierra Leone.

Methods
We conducted a nationwide cross-sectional study among 358 EVD survivors between January and August 2018. We used a multistage sampling method to recruit EVD survivors, and the RAND 36-Item Health Survey item was used to assess the HRQoL. Data were analysed using descriptive statistics and multiple linear regression.

Results
When comparing by each dimension in relation to their respective summary scores, role limitation physical [0.00 (50.00)] and role limitation emotional [0.00 (33.33)] were the most affected physical health and mental health domains among EVD survivors respectively. EVD survivors who were older (β = − 3.90, 95% CI − 6.47 to − 1.32, p = 0.003), had no formal education (β = − 2.80, 95% CI − 5.16 to − 0.43, p = 0.021), experienced a unit increase in the number of post-Ebola symptoms (β = − 1.08, 95% CI − 1.74 to − 0.43, p < 0.001) and experienced a unit increase in enacted stigma (β = − 2.61, 95% CI − 4.02 to − 1.20, p < 0.001) were more likely to report a decreased level of physical health. EVD survivors who experienced a unit increase in the time spent in the Ebola treatment centre (β = − 0.60, 95% CI − 0.103 to − 0.18, p = 0.006) and those who experienced a unit increase in enacted Stigma were more likely to report decreased levels of mental health (β = − 1.50, 95% CI − 2.67 to − 0.33, p = 0.012).

Conclusion
Sociodemographic, health-related, and psycho-social factors were significantly associated with decrease levels of HRQoL. Our findings improve our understanding of the factors that might influence the HRQoL and suggest the need for EVD survivors to be provided with a comprehensive healthcare package that caters for their physical and mental health needs.
Blood cholesterol-to-lymphocyte ratio as a novel prognostic marker to predict postoperative overall survival in patients with colorectal cancer
Authors: Zhou Siyu , He Qian , Sheng Nengquan , Gong Jianfeng , Ren Jiazi , Wang Zhigang 
Published: January 2022

AbstractBackgroundLipid disequilibrium and systemic inflammation are reported to correlate with tumorigenesis and development of colorectal cancer (CRC). We construct the novel biomarker cholesterol-to-lymphocyte ratio (CLR) to reflect the synergistic effect of cholesterol metabolism and inflammation on CRC outcomes. This study aims to investigate the clinical significance of CLR and establish a prognostic model for CRC.MethodsOur study retrospectively enrolled 223 CRC patients who underwent curative surgical resection. The Kaplan-Meier method was employed to estimate the overall survival (OS) rates, and the association between serological biomarkers and survival was assessed with a log-rank test. Cox proportional hazard regression was applied in the univariate and multivariate analyses to identify independent prognostic factors, which were then used to develop a predictive nomogram model for OS in CRC. The nomogram was evaluated by theC-index, receiver operator characteristic curve (ROC) analysis, and calibration plot. All cases were grouped into three stratifications according to the total risk points calculated from the nomogram, and the difference in OS between them was assessed with the Kaplan-Meier method.ResultsAt the end of the study, death occurred in 47 (21%) cases. Patients with low CLR (< 3.23) had significantly prolonged survival (P< 0.001). Multivariate analyses revealed that N stage (P< 0.001), harvested lymph nodes (P= 0.021), and CLR (P= 0.005) were independent prognostic factors for OS and a prognostic nomogram was established based on these variables. The nomogram showed good calibration and predictive performance with a superiorC-index than TNM stage (0.755 (0.719–0.791) vs. 0.663 (0.629–0.697),P= 0.001). Patients of different risk stratifications based on the total score of nomogram showed distinct survival (P< 0.001).ConclusionsThe nomogram based on CLR and other clinical features can be used as a potentially convenient and reliable tool in predicting survival in patients with CRC.
Conceptualizing and implementing a health workforce registry in Nigeria
Authors: Okoroafor Sunny C. , Oaiya Agbonkhese I. , Oviaesu David , Ahmat Adam , Osubor Martin , Nyoni Jennifer 
Published: January 2022

Abstract
Background
Nigeria’s health sector aims to ensure that the right number of health workers that are qualified, skilled, and distributed equitably, are available for quality health service provision at all levels. Achieving this requires accurate and timely health workforce information. This informed the development of the Nigeria Health Workforce Registry (NHWR) based on the global, regional, and national strategies for strengthening the HRH towards achieving universal health coverage. This case study describes the process of conceptualizing and establishing the NHWR, and discusses the strategies for developing sustainable and scalable health workforce registries.

Case presentation
In designing the NHWR, a review of existing national HRH policies and guidelines, as well as reports of previous endeavors was done to learn what had been done previously and obtain the views of stakeholders on how to develop a scalable and sustainable registry. The findings indicated the need to review the architecture of the registry to align with other health information systems, develop a standardized data set and guidance documents for the registry including a standard operating procedure to ensure that a holistic process is adopted in data collection, management and use nationally. Learning from the findings, a conceptual framework was developed, a registry managed centrally by the Federal Ministry of Health was developed and decentralized, a standardized tool based on a national minimum data was developed and adopted nationally, a registry prototype was developed using iHRIS Manage and the registry governance functions were integrated into the health information system governance structures. To sustain the functionality of the NHWR, the handbook of the NHWR that comprised of an implementation guide, the standard operating procedure, and the basic user training manual was developed and the capacity of government staff was built on the operations of the registry.

Conclusion
In establishing a functional and sustainable registry, learning from experiences is essential in shaping acceptable, sustainable, and scalable approaches. Instituting governance structures that include and involve policymakers, health managers and users is of great importance in the design, planning, implementation, and decentralization stages. In addition, developing standardized tools based on the health system's needs and instituting supportable mechanisms for data flow and use for policy, planning, development, and management is essential.
Policy options for strengthening evidence-informed health policy-making in Iran: overall SASHA project findings
Authors: Majdzadeh Reza , Sajadi Haniye Sadat , Yazdizadeh Bahareh , Doshmangir Leila , Ehsani-Chimeh Elham , Mahdavi Mahdi , Mehrdad Neda , Lavis John , Nikooee Sima , Mohtasham Farideh , Mohseni Mahsa , Akbari Paria , Asgardoon Mohammad Hossein , Rezaei Niloofar , Neyazi Narges , Ghaffarifar Saeideh , Haghdoost Ali Akbar , Khodayari-Zarnaq Rahim , Mosadeghrad Ali Mohammad , Pourabbasi Ata , Rafinejad Javad , Toyserkanamanesh Reza 
Published: January 2022

Abstract
Background
The institutionalization of evidence-informed health policy-making (EIHP) is complex and complicated. It is complex because it has many players and is complicated because its institutionalization will require many changes that will be challenging to make. Like many other issues, strengthening EIHP needs a road map, which should consider challenges and address them through effective, harmonized and contextualized strategies. This study aims to develop a road map for enhancing EIHP in Iran based on steps of planning.

Methods
This study consisted of three phases: (1) identifying barriers to EIHP, (2) recognizing interventions and (3) measuring the use of evidence in Iran's health policy-making. A set of activities was established for conducting these, including foresight, systematic review and policy dialogue, to identify the current and potential barriers for the first phase. For the second phase, an evidence synthesis was performed through a scoping review, by searching the websites of benchmark institutions which had good examples of EIHP practices in order to extract and identify interventions, and through eight policy dialogues and two broad opinion polls to contextualize the list of interventions. Simultaneously, two qualitative-quantitative studies were conducted to design and use a tool for assessing EIHP in the third phase.

Results
We identified 97 barriers to EIHP and categorized them into three groups, including 35 barriers on the “generation of evidence” (push side), 41 on the “use of evidence” (pull side) and 21 on the “interaction between these two” (exchange side). The list of 41 interventions identified through evidence synthesis and eight policy dialogues was reduced to 32 interventions after two expert opinion polling rounds. These interventions were classified into four main strategies for strengthening (1) the education and training system (6 interventions), (2) the incentives programmes (7 interventions), (3) the structure of policy support organizations (4 interventions) and (4) the enabling processes to support EIHP (15 interventions).

Conclusion
The policy options developed in the study provide a comprehensive framework to chart a path for strengthening the country’s EIHP considering both global practices and the context of Iran. It is recommended that operational plans be prepared for road map interventions, and the necessary resources provided for their implementation. The implementation of the road map will require attention to the principles of good governance, with a focus on transparency and accountability.
A budget impact analysis of substituting sitagliptin with liraglutide in type 2 diabetes from a private health insurance perspective in Egypt
Authors: Elsisi Gihan Hamdy , Afify Ayman , Abgad Ashraf , Zakaria Ibtissam , Nasif Nabil , Ibrahim Hani Naiem , Raafat Nabil , Carapinha João L. 
Published: January 2022

Abstract
Introduction
Type 2 diabetes mellitus causes a sizable burden globally from both health and economic points of view. This study aimed to assess the budget impact of substituting sitagliptin with liraglutide versus other glucose-lowering drugs from the private health insurance perspective in Egypt over a 3-year time horizon.

Methods
Two budget impact models were compared with the standard of care (metformin, pioglitazone, gliclazide, insulin glargine, repaglinide, and empagliflozin) administered in addition to liraglutide or sitagliptin versus the standard of care with placebo. A gradual market introduction of liraglutide or sitagliptin was assumed, and the existing market shares for the other glucose-lowering drugs were provided and validated by the Expert Panel. The event rates were extracted from the LEADER and TECOS trials. Direct and mortality costs were measured. Sensitivity analyses were performed.

Results
The estimated target population of 120,574 type 2 diabetic adult patients was associated with cardio vascular risk. The budget impact per patient per month for liraglutide is EGP29 ($6.7), EGP39 ($9), and EGP49 ($11.3) in the 1st, 2nd, and 3rd years, respectively. The budget impact per patient per month for sitagliptin is EGP11 ($2.5), EGP14 ($3.2), and EGP18 ($4.1) in the 1st, 2nd, and 3rd years, respectively. Furthermore, adoption of liraglutide resulted in 203 fewer deaths and 550 avoided hospitalizations, while sitagliptin resulted in 43 increased deaths and 14 avoided hospitalizations. The treatment costs of liraglutide use are mostly offset by substantial savings due to fewer cardiovascular-related events, avoided mortality and avoided hospitalizations over 3 years.

Conclusion
Adding liraglutide resulted in a modest budget impact, suggesting that the upfront drug costs were offset by budget savings due to fewer cardiovascular-related complications and deaths avoided compared to the standard of care. Sitagliptin resulted in a small budget impact but was associated with increased deaths and fewer hospitalizations avoided.
A comparison of approaches to measuring maternal mortality in Bangladesh, Mozambique, and Bolivia
Authors: Singh Kavita , Li Qingfeng , Ahsan Karar Zunaid , Curtis Sian , Weiss William 
Published: January 2022

Abstract
Background
Many low- and middle-income countries cannot measure maternal mortality to monitor progress against global and country-specific targets. While the ultimate goal for these countries is to have complete civil registrations systems, other interim strategies are needed to provide timely estimates of maternal mortality.

Objective
The objective is to inform on potential options for measuring maternal mortality.

Methods
This paper uses a case study approach to compare methodologies and estimates of pregnancy-related mortality ratio (PRMR)/maternal mortality ratio (MMR) obtained from four different data sources from similar time periods in Bangladesh, Mozambique, and Bolivia—national population census; post-census mortality survey; household sample survey; and sample vital registration system (SVRS).

Results
For Bangladesh, PRMR from the 2011 census falls closely in line with the 2010 household survey and SVRS estimates, while SVRS’ MMR estimates are closer to the PRMR estimates obtained from the household survey. Mozambique's PRMR from household survey method is comparable and shows an upward trend between 1994 and 2011, whereas the post-census mortality survey estimated a higher MMR for 2007. Bolivia's DHS and post-census mortality survey also estimated comparable MMR during 1998–2003.

Conclusions
Overall all these data sources presented in this paper have provided valuable information on maternal mortality in Bangladesh, Mozambique, and Bolivia. It also outlines recommendations to estimate maternal mortality based on the advantages and disadvantages of several approaches.

Contribution
Recommendations in this paper can help health administrators and policy planners in prioritizing investment for collecting reliable and contemporaneous estimates of maternal mortality while progressing toward a complete civil registration system.
Disaggregating proportional multistate lifetables by population heterogeneity to estimate intervention impacts on inequalities
Authors: Andersen Patrick , Mizdrak Anja , Wilson Nick , Davies Anna , Bablani Laxman , Blakely Tony 
Published: January 2022

AbstractBackgroundSimulation models can be used to quantify the projected health impact of interventions. Quantifying heterogeneity in these impacts, for example by socioeconomic status, is important to understand impacts on health inequalities. We aim to disaggregate one type of Markov macro-simulation model, the proportional multistate lifetable, ensuring that under business-as-usual (BAU) the sum of deaths across disaggregated strata in each time step returns the same as the initial non-disaggregated model. We then demonstrate the application by deprivation quintiles for New Zealand (NZ), for: hypothetical interventions (50% lower all-cause mortality, 50% lower coronary heart disease mortality) and a dietary intervention to substitute 59% of sodium with potassium chloride in the food supply.MethodsWe developed a disaggregation algorithm that iteratively rescales mortality, incidence and case-fatality rates by time-step of the model to ensure correct total population counts were retained at each step. To demonstrate the algorithm on deprivation quintiles in NZ, we used the following inputs: overall (non-disaggregated) all-cause mortality & morbidity rates, coronary heart disease incidence & case fatality rates; stroke incidence & case fatality rates. We also obtained rate ratios by deprivation for these same measures. Given all-cause and cause-specific mortality rates by deprivation quintile, we derived values for the incidence, case fatality and mortality rates for each quintile, ensuring rate ratios across quintiles and the total population mortality and morbidity rates were returned when averaged across groups. The three interventions were then run on top of these scaled BAU scenarios.ResultsThe algorithm exactly disaggregated populations by strata in BAU. The intervention scenario life years and health adjusted life years (HALYs) gained differed slightly when summed over the deprivation quintile compared to the aggregated model, due to the stratified model (appropriately) allowing for differential background mortality rates by strata. Modest differences in health gains (HALYs) resulted from rescaling of sub-population mortality and incidence rates to ensure consistency with the aggregate population.ConclusionPolicy makers ideally need to know the effect of population interventions estimated both overall, and by socioeconomic and other strata. We demonstrate a method and provide code to do this routinely within proportional multistate lifetable simulation models and similar Markov models.
Exosomes: the key of sophisticated cell–cell communication and targeted metastasis in pancreatic cancer
Authors: Zhang Huan , Xing Juan , Dai Zhujiang , Wang Daorong , Tang Dong 
Published: January 2022

AbstractPancreatic cancer is one of the most common malignancies. Unfortunately, the lack of effective methods of treatment and diagnosis has led to poor prognosis coupled with a very high mortality rate. So far, the pathogenesis and progression mechanisms of pancreatic cancer have been poorly characterized. Exosomes are small vesicles secreted by most cells, contain lipids, proteins, and nucleic acids, and are involved in diverse functions such as intercellular communications, biological processes, and cell signaling. In pancreatic cancer, exosomes are enriched with multiple signaling molecules that mediate intercellular communication with control of immune suppression, mutual promotion between pancreas stellate cells and pancreatic cancer cells, and reprogramming of normal cells. In addition, exosomes can regulate the pancreatic cancer microenvironment and promote the growth and survival of pancreatic cancer. Exosomes can also build pre-metastatic micro-ecological niches and facilitate the targeting of pancreatic cancer. The ability of exosomes to load cargo and target allows them to be of great clinical value as a biomarker mediator for targeted drugs in pancreatic cancer.