bluuebunny/crossref_metadata_2025_split huggingface dataset:
Omega-3 fatty acids impair miR-1-3p-dependent Notch3 down-regulation and alleviate sepsis-induced intestinal injury
Authors: Chen You-Lian , Xie Yin-Jing , Liu Zhen-Mi , Chen Wei-Bu , Zhang Ru , Ye Hong-Xing , Wang Wei , Liu Xue-Yan , Chen Huai-Sheng 
Published: January 2022

Abstract
Background
Sepsis is a troublesome syndrome that can cause intestinal injury and even high mortality rates. Omega-3 fatty acids (FAs) are known to protect against intestinal damage. Accordingly, the current study set out to explore if omega-3 FAs could affect sepsis-induced intestinal injury with the involvement of the microRNA (miR)-1-3p/Notch3-Smad axis.

Methods
First, cecal ligation and perforation (CLP) was performed to establish septic mouse models in C57BL/6J mice, and mouse intestinal epithelial MODE-K cells were induced by lipopolysaccharide (LPS) to establish sepsis cell models. The CLP-induced septic mice or LPS-exposed cells were subjected to treatment with Omega-3 FAs and activin (Smad signaling activator), miR-1-3p inhibitor and over-expressed/short hairpin RNA (oe-/sh)-Notch3 to explore their roles in inflammation, intestinal oxidative stress and cell apoptosis. A dual-luciferase reporter gene assay was further performed to verify the regulatory relationship between miR-1-3p and Notch3.

Results
Omega-3 FAs inhibited CLP-induced intestinal injury and ameliorated LPS-induced intestinal epithelial cell injury by down-regulating miR-1-3p, as evidenced by decreased levels of tumor necrosis factor-α, interleukin-1β (IL-1β) and IL-6, in addition to diminished levels of reactive oxygen species, malondialdehyde levels and superoxide dismutase activity. Furthermore, miR-1-3p could down-regulate Notch3, which inactivated the Smad pathway.

Conclusion
Collectively, our findings indicated that omega-3 FAs elevate the expression of Notch3 by down-regulating miR-1-3p, and then blocking the Smad pathway to alleviate intestinal epithelial inflammation and oxidative stress injury caused by sepsis.
Implementation of motivational interviewing in the general practice setting: a qualitative study
Authors: Boom Saskia M , Oberink Riëtta , Zonneveld Abigail J E , van Dijk Nynke , Visser Mechteld R M 
Published: January 2022

Abstract
Background
General Practitioners (GPs) and Practice Nurses (PNs) collaboratively play an important role in preventing and monitoring chronic diseases. They are trained in Motivational Interviewing (MI), which is a communication style to intrinsically motivate patients to a healthier lifestyle. However, being trained in MI skills does not necessarily mean that it is implemented in daily practice so patients actually benefit. The aim of this study is to identify factors that facilitate or impede the implementation of MI in General Practice.

Methods
A total of 152 participants (93 GP-trainees and 59 PN-trainees) who were trained in MI completed a questionnaire regarding the implementation of MI. Semi-structured interviews (N = 17) were conducted with GPs and PNs (ranging from almost graduated to highly experienced) who were selected through the process of maximum variation sampling. The interview guide was based on the five-stage implementation model of Grol and Wensing.

Results
Thirteen factors that influence the implementation of MI in General Practice were identified. They can be allocated to three categories: (1) setting factors such as time, (2) GP/PN factors such as self-efficacy, and (3) patient factors such as cultural background.

Conclusions
Overall, GPs and PNs considered MI to be useful and part of their professional responsibility. Most difficulties become apparent in stage 4 (change: applying MI skills in practice) and 5 (consolidation: integrating MI into daily routine and embedment in organisation) of Grol and Wensing’s model. Therefore, it is important that training does not only focus on MI skills. It is essential to pay explicit attention to the factors that impact implementation, as well as the appropriate tools to tackle the barriers. These insights can help trainers to effectively support GPs and PNs to apply and maintain their MI skills in daily practice.
Chronic kidney disease mediates cardiac dysfunction associated with increased resident cardiac macrophages
Authors: Mawhin M. A. , Bright R. G. , Fourre J. D. , Vloumidi E. I. , Tomlinson J. , Sardini A. , Pusey C. D. , Woollard K. J. 
Published: January 2022

AbstractBackgroundThe leading cause of death in end-stage kidney disease is related to cardiovascular disease. Macrophages are known to be involved in both chronic kidney disease (CKD) and heart failure, however their role in the development of cardiorenal syndrome is less clear. We thus sought to investigate the role of macrophages in uremic cardiac disease.MethodsWe assessed cardiac response in two experimental models of CKD and tested macrophage and chemokine implication in monocytopenic CCR2−/−and anti-CXCL10 treated mice. We quantified CXCL10 in human CKD plasma and tested the response of human iPSC-derived cardiomyocytes and primary cardiac fibroblasts to serum from CKD donors.ResultsWe found that reduced kidney function resulted in the expansion of cardiac macrophages, in particular through local proliferation of resident populations. Influx of circulating monocytes contributed to this increase. We identified CXCL10 as a crucial factor for cardiac macrophage expansion in uremic disease. In humans, we found increased plasma CXCL10 concentrations in advanced CKD, and identified the production of CXCL10 in cardiomyocytes and cardiac fibroblasts.ConclusionsThis study provides new insight into the role of the innate immune system in uremic cardiomyopathy.
Criteria for identification of advanced Parkinson’s disease: the results of the Italian subgroup of OBSERVE-PD observational study
Authors: Stefani Alessandro , Tessitore Alessandro , Tambasco Nicola , Cossu Giovanni , Ceravolo Maria Gabriella , Defazio Giovanni , Morgante Francesca , Ramat Silvia , Melzi Gabriella , Gualberti Giuliana , Merolla Rocco , Onuk Koray , Lopiano Leonardo 
Published: January 2022

Abstract
Background
Frequency of Advanced Parkinson’s Disease (APD) and its clinical characteristics are still not well defined. Here, we aimed to assess APD prevalence in the Italian OBSERVE-PD cohort, as well as treatment eligibility to device-aided therapies (DAT), and to compare the APD clinical judgment with the established Delphi criteria.

Methods
This sub-group analysis of the OBSERVE-PD study was performed on patients enrolled by 9 Movement Disorders centers in Italy. Motor and non-motor symptoms, PD characteristics, activities of daily living, and quality of life were assessed. Patient eligibility for DAT, response to current PD treatments, referral process, and the concordance between APD physician’s judgment and Delphi criteria were also assessed.

Results
According to physician’s judgment, 60 out of 140 patients (43%) had APD. The correlation between physician’s judgment and the overall APD Delphi criteria was substantial (K = 0.743; 95%CI 0.633–0.853), mainly driven by a discrete concordance found for the presence of ≥ 2 h of daily OFF time, presence of troublesome dyskinesia, ≥ 5 times daily oral levodopa dosing, and activities of daily living limitation. Forty-four (73%) APD patients were considered eligible to DAT but only 18 of them (41%) used these therapies, while most patients, independently from their eligibility, continued to use 3–5 oral daily medications, due to fear of invasive solutions and need to have a longer time to decide.

Conclusion
APD was frequent in the Italian OBSERVE-PD population. DAT in the eligible APD population proved to be underused, in spite of unsatisfactory symptoms control with oral medications in 67% of patients.
Geographical variation and predictors of zero utilization for a standard maternal continuum of care among women in Ethiopia: a spatial and geographically weighted regression analysis
Authors: Melaku Mequannent Sharew , Aemro Agazhe , Aychiluhm Setognal Birara , Muche Amare , Bizuneh Gizachew Kassahun , Kebede Shimels Derso 
Published: January 2022

Abstract
Background
Maintaining and effectively utilizing maternal continuum of care could save an estimated 860,000 additional mothers and newborn lives each year. In Ethiopia, the number of maternal and neonatal deaths occurred during pregnancy, childbirth, and the postpartum period was very high. It is indisputable that area-based heterogeneity of zero utilization for a standard maternal continuum of care is critical to improve maternal and child health interventions. However, none of the previous studies explored the spatial distribution of zero utilization for maternal continuum of care. Hence, this study was aimed to explore geographical variation and predictors of zero utilization for a standard maternal continuum of care among women in Ethiopia.

Methods
A total of 4178 women who gave birth five years preceding the 2016 Ethiopian demographic and health survey were included. ArcGIS version 10.7, SaT Scan version 9.6, and GWR version 4.0 Software was used to handle mapping, hotspot, ordinary least square, Bernoulli model analysis, and to model spatial relationships. Finally, a statistical decision was made at a p-value< 0.05 and at 95% confidence interval.

Main findings
The proportion of mothers who had zero utilization of a standard maternal continuum of care was 48.8% (95% CI: 47.3–50.4). Hot spot (high risk) regions for zero utilization of maternal continuum of care was detected in Afder, Warder, Korahe and Gode Zones of Somali region and West Arsi Zone of Oromia region. Respondents who had poor wealth index, uneducated mothers, and mothers who declared distance as a big problem could increase zero utilization of maternal continuum of care by 0.24, 0.27, and 0.1 times.

Conclusion
Five women out of ten could not utilize any components of a standard maternal continuum of care. Hot spot (high risk) areas was detected in Afder, Warder, Korahe and Gode Zones of Somali region and West Arsi Zone of Oromia region. Poor wealth index, uneducated mothers, and mothers who declare distance as a big problem were factors significantly associated with zero utilization of maternal continuum of care. Thus, geographical based intervention could be held to curve the high prevalence of zero utilization of maternal continuum of care.
The expression and survival significance of sodium glucose transporters in pancreatic cancer
Authors: Du Jiali , Gu Jichun , Deng Junyuan , Kong Lei , Guo Yujie , Jin Chen , Bao Yun , Fu Deliang , Li Ji 
Published: January 2022

Abstract
Background
Sodium glucose transporters (SGLTs) play vital roles in glucose uptake in many solid cancers, including pancreatic cancer (PC). However, their expression profile in pancreatic cancer and correlation with prognosis are not clear. Thus, we aimed to analyse the expression profile and prognostic significance of SGLT-1 and SGLT-2 in PC.

Methods
Eighty-eight patients with pancreatic ductal adenocarcinoma (PDAC) undergoing surgery in Huashan Hospital, Fudan University, from July 2017 to June 2020 were enrolled in the study. Specimens for immunohistochemistry were obtained through surgical resection. Bioinformatics analysis was performed based on the Gene Expression Omnibus (GEO), Oncomine and The Cancer Genome Atlas (TCGA) databases. The statistics were calculated using IBM SPSS Statistics, version 20 and R 4.1.1. P values lower than 0.05 were considered to indicate statistical significance.

Results
SGLT-1 but not SGLT-2 was significantly overexpressed in PDAC. Survival analysis showed that the median overall survival (OS) and progression-free survival (PFS) of patients with high SGLT-1 expression were significantly longer than that of patients with low SGLT-1 expression. Cox regression indicated that high SGLT-1 expression was an independent predictor for a better prognosis, while residual tumour status (R1 and R2) was an independent risk factor for a poor prognosis. Finally, PDZK1-interacting protein 1 (PDZK1IP1), a protein participating in the generation of reactive oxygen species, was overexpressed in PDAC and its expression was significantly correlated with SGLT-1.

Conclusions
SGLT-1 but not SGLT-2 was overexpressed in PDAC, and the overexpression of SGLT-1 could be a predictor of a better prognosis. Residual tumour status (R1 and R2) was a risk factor for poor prognosis and disease progression.
Is having a 20-minute neighbourhood associated with eating out behaviours and takeaway home delivery? A cross-sectional analysis of ProjectPLAN
Authors: Oostenbach Laura H. , Lamb Karen E. , Thornton Lukar E. 
Published: January 2022

Abstract
Background
Through improved service provision and accessibility, 20-min neighbourhoods (20MNs) aim to enable people to meet most of their daily (non-work) needs within 20 min from home. Associations between 20MNs and food practices remain unknown. This study examines links with the frequency and location of eating out behaviours as well as the frequency of home food delivery.

Methods
This cross-sectional study used data from 769 adults from the Places and Locations for Activity and Nutrition study (ProjectPLAN) conducted in Melbourne and Adelaide, Australia, between 2018 and 2019. Outcomes were 1) visit frequency to i) cafés, ii) restaurants, bars or bistros, iii) major chain fast food outlets and iv) takeaway outlets to purchase food; 2) total number of different types of out-of-home food outlets visited; 3) use frequency of home food delivery services; 4) distance from home to the most frequented out-of-home food outlets. Exposure was whether participants had a 20MN (areas with high service/amenity provision) or a non-20MN (areas with low service/amenity provision). Ordinal regression models were fitted for the frequency outcomes. Poisson regression models were fitted for the number of different outlet types. Linear and spatial regression models were fitted for the distance outcomes.

Results
Results suggested no differences in frequency of visitations to out-of-home food outlets and use of food delivery services between those with a 20MN and those with a non-20MN. Yet, those with a 20MN were more likely to use a greater number of different types of outlets on a weekly basis. Where a regular eating out location was reported, it was nearer to home for those with a 20MN.

Conclusions
This study provides evidence supportive of 20MNs potentially facilitating more localised food practices, however, 20MNs may also encourage greater cumulative frequency of meals out across a variety of out-of-home food providers.
A CRISPR toolbox for generating intersectional genetic mouse models for functional, molecular, and anatomical circuit mapping
Authors: Lusk Savannah J. , McKinney Andrew , Hunt Patrick J. , Fahey Paul G. , Patel Jay , Chang Andersen , Sun Jenny J. , Martinez Vena K. , Zhu Ping Jun , Egbert Jeremy R. , Allen Genevera , Jiang Xiaolong , Arenkiel Benjamin R. , Tolias Andreas S. , Costa-Mattioli Mauro , Ray Russell S. 
Published: January 2022

Abstract
Background
The functional understanding of genetic interaction networks and cellular mechanisms governing health and disease requires the dissection, and multifaceted study, of discrete cell subtypes in developing and adult animal models. Recombinase-driven expression of transgenic effector alleles represents a significant and powerful approach to delineate cell populations for functional, molecular, and anatomical studies. In addition to single recombinase systems, the expression of two recombinases in distinct, but partially overlapping, populations allows for more defined target expression. Although the application of this method is becoming increasingly popular, its experimental implementation has been broadly restricted to manipulations of a limited set of common alleles that are often commercially produced at great expense, with costs and technical challenges associated with production of intersectional mouse lines hindering customized approaches to many researchers. Here, we present a simplified CRISPR toolkit for rapid, inexpensive, and facile intersectional allele production.

Results
Briefly, we produced 7 intersectional mouse lines using a dual recombinase system, one mouse line with a single recombinase system, and three embryonic stem (ES) cell lines that are designed to study the way functional, molecular, and anatomical features relate to each other in building circuits that underlie physiology and behavior. As a proof-of-principle, we applied three of these lines to different neuronal populations for anatomical mapping and functional in vivo investigation of respiratory control. We also generated a mouse line with a single recombinase-responsive allele that controls the expression of the calcium sensor Twitch-2B. This mouse line was applied globally to study the effects of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on calcium release in the ovarian follicle.

Conclusions
The lines presented here are representative examples of outcomes possible with the successful application of our genetic toolkit for the facile development of diverse, modifiable animal models. This toolkit will allow labs to create single or dual recombinase effector lines easily for any cell population or subpopulation of interest when paired with the appropriate Cre and FLP recombinase mouse lines or viral vectors. We have made our tools and derivative intersectional mouse and ES cell lines openly available for non-commercial use through publicly curated repositories for plasmid DNA, ES cells, and transgenic mouse lines.
CircPVT1: a pivotal circular node intersecting Long Non-Coding-PVT1 and c-MYC oncogenic signals
Authors: Palcau Alina Catalina , Canu Valeria , Donzelli Sara , Strano Sabrina , Pulito Claudio , Blandino Giovanni 
Published: January 2022

AbstractThe role of circular RNAs in oncogenesis has begun to be widely studied in recent years, due to the significant impact that these molecules have in disease pathogenesis, as well as their potential for the future of innovative therapies. Moreover, due to their characteristically circular shape, circular RNAs are very resistant molecules to RNA degradation whose levels are easily assessed in body fluids. Accordingly, they represent an opportunity for the discovery of new diagnostic and prognostic markers in a wide range of diseases. Among circular RNAs, circPVT1 is a rather peculiar one that originates from the circularization of the exon 2 of the PVT1 gene that encodes a pro-tumorigenic long non-coding RNA named lncPVT1. There are a few examples of circular RNAs that derive from a locus producing another non-coding RNA. Despite their apparent transcriptional independence, which occurs using two different promoters, a possible synergistic effect in tumorigenesis cannot be excluded considering that both have been reported to correlate with the oncogenic phenotype. This complex mechanism of regulation appears to also be controlled by c-MYC. Indeed, the PVT1 locus is located only 53 Kb downstream c-MYC gene, a well-known oncogene that regulates the expression levels of about 15% of all genes. Here, we review circPVT1 origin and biogenesis highlighting the most important mechanisms through which it plays a fundamental role in oncogenesis, such as the well-known sponge activity on microRNAs, as well as its paradigmatic interactome link with lncPVT1 and c-MYC expression.
How to make the best use of the workload indicators of staffing needs method in determining the proportion of time spent in each of the workload components and its implication in decision making: the experience of the Sultanate of Oman
Authors: Mohamed Nazar , Al-Lawati Nahida 
Published: January 2022

Abstract
Background
The Ministry of Health in the Sultanate of Oman decided to have better distribution of the health workforce among all health facilities through evidenced-based staffing norms. Four directorates worked together to develop the staffing norms through making use of the workload indicators of staffing needs (WISN) method. The aim of this study is to describe the process of applying the WISN method in Primary Health Care institutions and how to make the best use of method in determining the proportion of time spent in each of the workload components and its implication in decision making.

Methods
The WISN was applied for five priority categories, namely, doctors, nurses, pharmacists, laboratory technicians, and radiology technicians at PHC institutions. The WISN ratio has been translated into workload pressure as a percentage through applying the formula [workload pressure as % (in case of shortage) = (1 − WISN ratio) × 100%]. While the proportion of time spent in each of the workload components was calculated through making use of the category allowance standard, the individual allowance standard to determine the time spent in support and additional activities. The sum is subtracted from 100% to give the time spent in the health service activities.

Results
Determining the workload pressure as a percent and its interpretation is based on the fact that one cadre or as a group can bear up to 10% of extra workload. Thus, managers can undertake sensible short-term arrangements or decisions in redistributing the cadres among the health facilities on expectation of deploying more staff.

Discussion
Careful and detailed analysis of the proportion of time spent in each of the workload components will allow to have better understanding of the context and dynamics of work.

Conclusion
Decision makers and planners can undertake rational short-term decisions in redistributing the cadres among the health facilities based on the workload pressure. In addition, they can as well as easily decide on the optimal proportions of time for each staff category, and hence choose what activities and tasks to be shifted or delegated to other staff category.
Workload assessment of medical doctors at primary health care centers in the Duhok governorate
Authors: Al-Dabbagh Samim Ahmed , Sulaiman Hushyar Musa , Abdulkarim Nazik Abdulrahman 
Published: January 2022

Abstract
Background
A shortage in human resources, particularly physicians, has become a challenge confronting health authorities in the Duhok governorate, as these resources are the key input for delivering health care. It has become necessary to identify the most appropriate scientifically sound method for having adequate staffing levels. This study aimed to forecast the required number of physicians to cope with the current workload at the main primary health care centers in the Duhok governorate.

Methods
A cross-sectional study was adopted to collect data for 1 full year. Data collection included both primary and secondary data sources. A semi-structured questionnaire was developed to obtain information every month from health centers on activities related to training and leaves. Data analysis was performed using Workload Indicators of Staffing Need software.

Results
Sixty-one primary health care centers met the final criteria for analysis. The study revealed physician shortages and inequity in the distribution of staffing. In these centers, 145 physicians lacked an adequate delivery of health services based on the workload imposed on them. The ‘workload indicators of staffing need’ ratio was 0.33, indicating high work pressure on medical doctors. Some centers offered more health care than others, but had fewer doctors based on the current staffing practices.

Conclusions
This study pointed out the importance for the public health sector and academic medical institutions to use Workload Indicators of Staffing Needs software in health policy administration to restructure their efforts to address the physician shortages and distribution imbalances at primary health care facilities.