bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol for a randomized controlled trial to test the acceptability and adherence to 6-months of walnut supplementation in Chinese adults at high risk of cardiovascular disease
Authors: Liu Yishu , Li Nan , Yan Ni , Pan Xiong-fei , Li Qiang , Micha Renata , Mozaffarian Dariush , Huffman Mark D. , Wang Yanfang , Neal Bruce , Tian Maoyi , Zhao Yi , Wu Jason H. Y. 
Published: January 2021

Abstract
Background
Consumption of nuts improves cardio-metabolic risk factors in clinical trials and relates to lower risk of cardiovascular disease (CVD) in prospective observational studies. However, there has not been an adequately powered randomized controlled trial to test if nuts supplementation actually reduces incident CVD. In order to establish the feasibility of such a trial, the current study aimed to assess the acceptability and adherence to long-term nut supplementation amongst individuals at high CVD risk in China.

Methods
This protocol described a 6-month trial performed in Ningxia Province in China among participants with a history of CVD or older age (female ≥65 years, male ≥60 years) with multiple CVD risk factors. Participants were randomized to control (received non-edible gift), low dose walnut (30 g/d), or high dose walnut (60 g/d) groups in a 1:1:1 ratio. Walnuts were provided at no cost to participants and could be consumed according to personal preferences. Follow-up visits were scheduled at 2 weeks, 3 months and 6 months. The primary outcome was fasting plasma alpha linolenic acid (ALA) levels used as an indicator of walnut consumption. Secondary outcomes included self-reported walnut intake from the 24 h dietary recalls. The target sample size of 210 provided 90% statistical power with two-sided alpha of 0.05 to detect a mean difference of 0.12% (as percent of total fatty acid) in plasma ALA between randomized groups.

Results
Two hundred and ten participants were recruited and randomized during October 2019. Mean age of participants was 65 years (SD = 7.3), 47% were females, and 94% had a history of CVD at baseline. Across the three study groups, participants had similar baseline demographic and clinical characteristics.

Discussion
This trial will quantify acceptability and adherence to long-term walnut supplementation in a Chinese population at high risk of CVD. The findings will support the design of a future large trial to test the effect of walnut supplementation for CVD prevention.

Trial registration
NCT04037943
Protocol version: v3.0 August 14 2019
District division administrative disaggregation data framework for monitoring leaving no one behind in the National Health Insurance Fund of Sudan: achieving sustainable development goals in 2030
Authors: Mansour Ashraf , Sirichotiratana Nithat , Viwatwongkasem Chukiat , Khan Mahmud , Srithamrongsawat Samrit 
Published: January 2021

Abstract
Background
The aim of this study is to monitor the concept of ‘leaving no one behind’ in the Sustainable Development Goals (SDGs) to track the implications of the mobilization of health care resources by the National Health Insurance Fund (NHIF) of Sudan.

Methods
A cross-sectional study was used to monitor ‘leaving no one behind’ in NHIF by analyzing the secondary data of the information system for the year 2016. The study categorized the catchment areas of health care centers (HCCS) according to district administrative divisions, which are neighborhood, subdistrict, district, and zero. The District Division Administrative Disaggregation Data (DDADD) framework was developed and investigated with the use of descriptive statistics, maps of Sudan, the Mann-Whitney test, the Kruskal-Wallis test and health equity catchment indicators. SPSS ver. 18 and EndNote X8 were also used.

Results
The findings show that the NHIF has mobilized HCCs according to coverage of the insured population. This mobilization protected the insured poor in high-coverage insured population districts and left those living in very low-coverage districts behind. The Mann-Whitney test presented a significant median difference in the utilization rate between catchment areas (P value < 0.001). The results showed that the utilization rate of the insured poor who accessed health care centers by neighborhood was higher than that of the insured poor who accessed by more than neighborhood in each state. The Kruskal-Wallis test of the cost of health care services per capita in each catchment area showed a difference (P value < 0.001) in the median between neighborhoods. The cost of health care services in low-coverage insured population districts was higher than that in high-coverage insured population districts.

Conclusion
The DDADD framework identified the inequitable distribution of health care services in low-density population districts leaves insured poor behind. Policymakers should restructure the equation of health insurance schemes based on equity and probability of illness, to distribute health care services according to needs and equity, and to remobilize resources towards districts left behind.
Applying a gender lens to understand pathways through care for acutely ill young children in Kenyan urban informal settlements
Authors: Muraya Kui , Ogutu Michael , Mwadhi Mercy , Mikusa Jennifer , Okinyi Maureen , Magawi Charity , Zakayo Scholastica , Njeru Rita , Haribondhu Sarma , Uddin Md. Fakhar , Marsh Vicki , Walson Judd L. , Berkley James , Molyneux Sassy 
Published: January 2021

Abstract
Background
In many African settings, gender strongly influences household treatment-seeking and decision-making for childhood illnesses. While mothers are often the primary engagers with health facilities, their independence in illness-related decisions is shaped by various factors. Drawing on a gender lens, we explored treatment-seeking pathways pre- and post-hospital admission for acutely ill young children living in low income settlements in Nairobi, Kenya; and the gendered impact of child illness both at the household and health system level.

Methods
Household members of 22 children admitted to a public hospital were interviewed in their homes several times post hospital discharge. In-depth interviews covered the child’s household situation, health and illness; and the family’s treatment-seeking choices and experiences. Children were selected from an observational cohort established by the Childhood Acute Illness and Nutrition (CHAIN) Network.

Results
Treatment-seeking pathways were often long and complex, with mothers playing the key role in caring for their children and in treatment decision-making. Facing many anxieties and dilemmas, mothers often consulted with significant influencers - primarily women - particularly where illnesses were prolonged or complex. In contrast to observations in rural African contexts, fathers were less prominent as influencers than (often female) neighbours, grandparents and other relatives. Mothers were sometimes blamed for their child’s condition at home and at health facilities. Children’s illness episode and associated treatment-seeking had significant gendered socio-economic consequences for households, including through mothers having to take substantial time off work, reduce their working hours and income, or even losing their jobs.

Conclusion
Women in urban low-income settings are disproportionately impacted by acute child illness and the related treatment-seeking and recovery process. The range of interventions needed to support mothers as they navigate their way through children’s illnesses and recovery include: deliberate engagement of men in child health to counteract the dominant perception of child health and care as a ‘female-domain’; targeted economic strategies such as cash transfers to safeguard the most vulnerable women and households, combined with more robust labour policies to protect affected women; as well as implementing strategies at the health system level to improve interactions between health workers and community members.
Does the separating of hospital revenue from drug sales reduce the burden on patients? Evidence from China
Authors: Li Lele , Yu Qiao 
Published: January 2021

Abstract
Background
Since 2015, all pilot cities of public hospital reform in China have allowed the zero-markup drug policy and implemented the policy of Separating of Hospital Revenue from Drug Sales (SHRDS). The objective of this study is to evaluate whether SHRDS policy reduces the burden on patients, and to identify the mechanism through which SHRDS policy affects healthcare expenditure.

Methods
In this study, we use large sample data of urban employee’s healthcare insurance in Chengdu, and adopt the difference in difference model (DID) to estimate the impact of the SHRDS policy on total healthcare expenditures and drug expenditure of patients, and to provide empirical evidence for deepening medical and health system reform in China.

Results
After the SHRDS policy’s implementation, the total healthcare expenditure kept growing, but the growth rate slowed down between 2014 to 2015. The total healthcare expenditure of patients decreased by only 0.6%, the actual reimbursement expenditure of patients decreased by 4.1%, the reimbursement ratio decreased by 2.6%. and the drugs expenditure dropped by 14.4%. However, the examinations expenditure increased by 18.2%, material expenditure increased significantly by 38.5%, and nursing expenditure increased by 12.7%.

Conclusions
After implementing the SHRDS policy, the significant reduction in drug expenditure led to more physicians inducing patients’ healthcare service needs, and the increased social healthcare burden was partially transferred to the patients’ personal economic burden through the decline in the reimbursement ratio. The SHRDS policy is not an effective way to control healthcare expenditure.
Dysbiosis of urine microbiota in obstructive urinary retention patients revealed by next-generation sequencing
Authors: Jiang Shan , Lu Saisai , Chen Xiaomin , Li Fengxia , Zhu Chengwei , Zheng Yuancai , Wang Xiaobing , Xu Shihao 
Published: January 2021

Abstract
Background
Urinary retention (UR) is a common urinary system disease can be caused by urinary tract obstruction with numerous reasons, however, the role of urine microbes in these disorders is still poorly understood. The aim of this study was to identify the urine microbial features of two common types of obstructive UR, caused by urinary stones or urinary tract tumors, with comparison to healthy controls.

Methods
Urine samples were collected from a cohort of 32 individuals with stone UR, 25 subjects with tumor UR and 25 healthy controls. The urine microbiome of all samples was analyzed using high-throughput 16S rRNA (16S ribosomal RNA) gene sequencing.

Results
We observed dramatically increased urine microbial richness and diversity in both obstructive UR groups compared to healthy controls. Despite different origins of UR, bacteria such as Pseudomonas, Acinetobacter and Sphingomonas were enriched, while Lactobacillus, Streptococcus, Gardnerella, Prevotella and Atopobium were decreased in both UR groups in comparison with healthy controls, exhibited an approximate urine microbial community and functional characteristics of two types of obstructive UR. Furthermore, disease classifiers were constructed using specific enriched genera in UR, which can distinguish stone UR or tumor UR patients from healthy controls with an accuracy of 92.29% and 97.96%, respectively.

Conclusion
We presented comprehensive microbial landscapes of two common types of obstructive urinary retention and demonstrated that urine microbial features of these patients are significantly different from that of healthy people. The urine microbial signatures would shed light on the pathogenesis of these types of urinary retention and might be used as potential classification tools in the future.
Two nanoformulations induce reactive oxygen species and immunogenetic cell death for synergistic chemo-immunotherapy eradicating colorectal cancer and hepatocellular carcinoma
Authors: Guo Jianfeng , Yu Zhuo , Sun Dandan , Zou Yifang , Liu Yun , Huang Leaf 
Published: January 2021

Abstract
Background
FOLFOX is a combinational regimen of folinic acid (FnA, FOL), fluorouracil (5-Fu, F) and oxaliplatin (OxP, OX), and has been long considered as the standard treatment of colorectal cancer (CRC) and hepatocellular carcinoma (HCC). Recent developments of nano delivery systems have provided profound promise for improving anticancer efficacy and alleviating side effects of FOLFOX. Previously, a nanoformulation (termed Nano-Folox) containing OxP derivative and FnA was developed in our laboratory using nanoprecipitation technique. Nano-Folox induced OxP-mediated immunogenic cell death (ICD)-associated antitumor immunity, which significantly suppressed tumor growth in the orthotopic CRC mouse model when administrated in combination with free 5-Fu.

Methods
A nanoformulation (termed Nano-FdUMP) containing FdUMP (5-Fu active metabolite) was newly developed using nanoprecipitation technique and used in combination with Nano-Folox for CRC and HCC therapies.

Results
Synergistic efficacy was achieved in orthotopic CRC and HCC mouse models. It resulted mainly from the fact that Nano-FdUMP mediated the formation of reactive oxygen species (ROS), which promoted the efficacy of ICD elicited by Nano-Folox. In addition, combination of Nano-Folox/Nano-FdUMP and anti-PD-L1 antibody significantly inhibited CRC liver metastasis, leading to long-term survival in mice.

Conclusion
This study provides proof of concept that combination of two nano delivery systems can result in successful FOLFOX-associated CRC and HCC therapies. Further optimization in terms of dosing and timing will enhance clinical potential of this combination strategy for patients.

Graphical abstract
LDL-cholesterol change and goal attainment following statin intensity titration among Asians in primary care: a retrospective cohort study
Authors: Fang Hao Sen Andrew , Gao Qiao , Lee Mong Li , Hsu Wynne , Tan Ngiap Chuan 
Published: January 2021

Abstract
Background
Clinical trials have demonstrated that either initiating or up-titrating a statin dose substantially reduce Low-Density Lipoprotein-Cholesterol (LDL-C) levels. However, statin adherence in actual practice tends to be suboptimal, leading to diminished effectiveness. This study aims to use real-world data to determine the effect on LDL-C levels and LDL-C goal attainment rates, when selected statins are titrated in Asian patients.

Methods
A retrospective cohort study over a 5-year period, from April 2014 to March 2019 was conducted on a cohort of multi-ethnic adult Asian patients with clinical diagnosis of Dyslipidaemia in a primary care clinic in Singapore. The statins were classified into low-intensity (LI), moderate-intensity (MI) and high-intensity (HI) groups according to the 2018 American College of Cardiology and American Heart Association (ACC/AHA) Blood Cholesterol Guidelines. Patients were grouped into “No statin”, “Non-titrators” and “Titrators” cohorts based on prescribing patterns. For the “Titrators” cohort, the mean percentage change in LDL-C and absolute change in LDL-C goal attainment rates were computed for each permutation of statin intensity titration.

Results
Among the cohort of 11,499 patients, with a total of 266,762 visits, there were 1962 pairs of LDL-C values associated with a statin titration. Initiation of LI, MI and HI statin resulted in a lowering of LDL-C by 21.6% (95%CI = 18.9–24.3%), 28.9% (95%CI = 25.0–32.7%) and 25.2% (95%CI = 12.8–37.7%) respectively. These were comparatively lower than results from clinical trials (30 to 63%). The change of LDL-C levels due to up-titration, down-titration, and discontinuation were − 12.4% to − 28.9%, + 13.2% to + 24.6%, and + 18.1% to + 32.1% respectively. The improvement in LDL-C goal attainment ranged from 26.5% to 47.1% when statin intensity was up-titrated.

Conclusion
In this study based on real-world data of Asian patients in primary care, it was shown that although statin titration substantially affected LDL-C levels and LDL-C goal attainment rates, the magnitude was lower than results reported from clinical trials. These results should be taken into consideration and provide further insight to clinicians when making statin adjustment recommendations in order to achieve LDL-C targets in clinical practice, particularly for Asian populations.
Synaptosomes: new vesicles for neuronal mitochondrial transplantation
Authors: Picone Pasquale , Porcelli Gaetana , Bavisotto Celeste Caruso , Nuzzo Domenico , Galizzi Giacoma , Biagio Pier Luigi San , Bulone Donatella , Di Carlo Marta 
Published: January 2021

Abstract
Background
Mitochondrial dysfunction is a critical factor in the onset and progression of neurodegenerative diseases. Recently, mitochondrial transplantation has been advised as an innovative and attractive strategy to transfer and replace damaged mitochondria. Here we propose, for the first time, to use rat brain extracted synaptosomes, a subcellular fraction of isolated synaptic terminal that contains mitochondria, as mitochondrial delivery systems.

Results
Synaptosome preparation was validated by the presence of Synaptophysin and PSD95. Synaptosomes were characterized in terms of dimension, zeta potential, polydispersity index and number of particles/ml. Nile Red or CTX-FITCH labeled synaptosomes were internalized in LAN5 recipient cells by a mechanism involving specific protein–protein interaction, as demonstrated by loss of fusion ability after trypsin treatment and using different cell lines. The loading and release ability of the synaptosomes was proved by the presence of curcumin both into synaptosomes and LAN5 cells. The vitality of mitochondria transferred by Synaptosomes was demonstrated by the presence of Opa1, Fis1 and TOM40 mitochondrial proteins and JC-1 measurements. Further, synaptosomes deliver vital mitochondria into the cytoplasm of neuronal cells as demonstrated by microscopic images, increase of TOM 40, cytochrome c, Hexokinase II mitochondrial proteins, and presence of rat mitochondrial DNA. Finally, by using synaptosomes as a vehicle, healthy mitochondria restored mitochondrial function in cells containing rotenone or CCCp damaged mitochondria.

Conclusions
Taken together these results suggest that synaptosomes can be a natural vehicle for the delivery of molecules and organelles to neuronal cells. Further, the replacement of affected mitochondria with healthy ones could be a potential therapy for treating neuronal mitochondrial dysfunction-related diseases.
Assessing the reliability and validity of the ICECAP-A instrument in Chinese type 2 diabetes patients
Authors: Xiong Yao , Wu Hongyan , Xu Judy 
Published: January 2021

Abstract
Purpose
We aimed to conduct psychometric tests for the Chinese version of ICECAP-A and compare the differences between ICECAP-A and EQ-5D-3L for patients with T2DM and explore the relationship between clinical conditions and ICECAP-A through diabetes-related clinical indicators.

Methods
Data were collected from a sample of 492 Chinese T2DM patients. The reliability and validity of the ICECAP-A were verified. Exploratory factor analysis (EFA), correlation analysis and regression analysis were conducted for both the ICECAP-A and EQ-5D-3L.

Results
Our results show that the Chinese version of ICECAP-A has good internal consistency with an overall Cronbach’s Alpha coefficient of 0.721. The mean scores of ICECAP-A and EQ-5D-3L are 0.85 vs. 0.94. A weak correlation (r = 0.116) was found between the ICECAP-A tariff and EQ-5D-3L utility. EFA showed that although the five dimensions of the ICECAP-A and EQ-5D-3L scales were loaded into two different factors respectively. However, the two scales captured different dimensions of quality of life and can complement each other. The ICECAP-A, EQ-5D-3L, and EQ-VAS scores showed differences across different socio-demographic characteristics and clinic conditions groups.

Conclusion
The Chinese version of the ICECAP-A capability instrument can be for assessing outcomes in adults with T2DM. It may capture more dimensions of QoL than traditional Health-related QoL (HRQoL) instruments and may be useful for economic evaluations of health care and social care for people with T2DM or other chronic diseases.
Factors influencing health behavior practice in patients with coronary artery diseases
Authors: Jung Ho Gi , Yang Ya Ki 
Published: January 2021

AbstractBackgroundThe purpose of this study was to investigate the relationships among cardiac rehabilitation knowledge, educational need and health behavior practice in patients with coronary artery disease and explain factors influencing health behavior practice.MethodThe research participants were 189 patients with coronary artery disease from general hospital located in Korea. Self-evaluation questionnaires were used to collect the data. Data was collected from January to May, 2020. Data were analyzed using descriptive statistics, independent t-test, one-way ANOVA, Pearson correlation coefficients and multiple regression with the SPSS 24.0 program.ResultsThere were significant positive relationships between cardiac rehabilitation knowledge and health behavior practice (r = .37,p < .001), and significant positive relationships between educational need and health behavior practice (r = .17,p = .022). Factors influencing health behavior practice were identified, the most critical predictive factor was age (≥80) (β = .52), followed by cardiac rehabilitation knowledge (β = .42), regular exercise (No) (β = −.25), family history (No) (β = .24), age (60-69) (β = .22), cohabitation (No) (β = −.20) and educational needs (β = .17). The explanation power of this model was 50% and it was statistically significant (F = 13.42,p < .001).ConclusionThis study suggests that cardiac rehabilitation knowledge and educational need should be considered in enhancing cardiac rehabilitation programs designed for patients with coronary artery disease.
Chinese pediatric Tuina on children with acute diarrhea: a randomized sham-controlled trial
Authors: Lu Taoying , Yin Lingjia , Chen Ruoqing , Zhang Huiyan , Cai Jianxiong , Li Meiling , Dai Lin , Zhu Conghao , Zhang Yongping , Xiang Feng , Wang Li , Li Lu , Wang Lixin , Wu Darong 
Published: January 2021

Abstract
Background
Pediatric Tuina has been
widely used in children with acute diarrhea in China. However, due to the lack of high-quality clinical evidence, the benefit of Tuina as a therapy is not clear. We aimed to assess the effect of pediatric Tuina compared with sham Tuina as an add-on therapy in addition to usual care for 0–6-year-old children with acute diarrhea.

Methods
Eighty-six participants aged 0–6 years with acute diarrhea were randomized to receive pediatric Tuina plus usual care (n = 43) or sham Tuina plus usual care (n = 43). The primary outcomes were days of diarrhea from baseline and times of diarrhea on day 3. Secondary outcomes included a global change rating (GCR) and the number of days when the stool characteristics returned to normal. Adverse events were assessed.

Results
Pediatric Tuina was associated with a reduction in times of diarrhea on day 3 compared with sham Tuina in both ITT (crude RR, 0.73 [95% CI, 0.59–0.91]) and PP analyses (crude RR, 0.66 [95% CI, 0.53–0.83]). However, the results were not significant when we adjusted for social demographic and clinical characteristics. No significant difference was found between groups in days of diarrhea, global change rating, or number of days when the stool characteristics returned to normal.

Conclusions
In children aged 0–6 years with acute diarrhea, pediatric Tuina showed significant effects in terms of reducing times of diarrhea compared with sham Tuina. Studies with larger sample sizes and adjusted trial designs are warranted to further evaluate the effect of pediatric Tuina therapy.

Trial registration
Clinicaltrials.gov, Identifier: NCT03005821, Data of registration: 2016-12-29.