bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of heart failure risk and medical costs between patients with type 2 diabetes mellitus treated with dapagliflozin and dipeptidyl peptidase-4 inhibitors: a nationwide population-based cohort study
Authors: Seong Jong-Mi , Kim Jong Joo , Kim Hae Jin , Sohn Hyun Soon 
Published: June 2020

Abstract
Background
Dapagliflozin is one of the novel glucose-lowering agents, which has recently been reported to reduce the risk of hospitalization for heart failure (hHF). The present study aimed to compare the differences between the risk of hHF after using dapagliflozin and dipeptidyl peptidase-4 inhibitors (DPP-4i) as second-line drugs for the treatment of type 2 diabetes mellitus using the latest nationwide population data in Korea. Additionally, we aimed to examine the impact of clinical outcomes on direct medical costs in the two groups.

Methods
The present population-based, retrospective cohort study was conducted using the nationwide claims data between September 01, 2014 and June 30, 2018. New users of dapagliflozin and DPP-4i were identified from the database and the differences in patients’ characteristics between the two groups were analyzed using propensity score-weighted analysis. Cox proportional hazards regression analysis was used to estimate the risk of hHF. A simple model was used for the estimation of direct medical costs for 3 years.

Results
In total, 23,147 patients in the dapagliflozin group and 237,187 patients in the DPP-4i group were selected for the analysis. The incidence rates of hHF were 3.86 and 6.79 per 1000 person-years in the dapagliflozin and DPP-4i groups, respectively. In the entire study population, the hazard ratio for hHF in the dapagliflozin group compared to the DPP-4i group was 0.58 (95% confidence interval 0.46–0.74), with 0.55 (95% confidence interval 0.41–0.74) among patients with underlying cardiovascular disease and 0.66 (95% confidence interval 0.46–0.95) among patients without underlying cardiovascular disease. The direct medical costs were $57,787 lower in the dapagliflozin group than in the DPP-4i group for 3 years.

Conclusions
This study showed that dapagliflozin lowers the risk for hHF and subsequently reduces direct medical costs compared to DPP-4i. The protective effect against hHF was more evident among patients with underlying cardiovascular disease.
Biomarker implication of kallikrein-related peptidases as prognostic tissue substrates of poor survival in colorectal cancer
Authors: Peng Qiliang , Shen Yi , Zhao Peifeng , Cheng Ming , Wu Yongyou , Zhu Yaqun 
Published: June 2020

AbstractBackgroundRecent studies have demonstrated that the kallikrein and kallikrein-related peptidases (KLKs) exhibit aberrant expression in patients with colorectal cancer (CRC) and might be considered as potential prognostic biomarkers of CRC. However, inconsistent findings have been reported, which promote us to summarize the global prognostic roles of KLKs for survival in CRC patients.MethodsEligible published studies were identified by searching electronic databases with several search strategies. The patients’ baseline characteristics and survival results were extracted from enrolled studies and pooled as combined hazard ratio (HR) with 95% confidence interval (95% CI) to estimate the effect size.ResultsA total of 25 and 22 eligible studies were included in the meta-analysis to evaluate the prognostic roles of KLKs on overall survival (OS) and disease-free survival (DFS), respectively. KLKs overexpression was significantly associated with worse OS (pooled HR = 1.43, 95% CI 1.27–1.60, P < 0.001) and short DFS (pooled HR = 1.35, 95% CI 1.21–1.51, P < 0.001). Importantly, subgroup and meta-regression analyses revealed the survival differences among different races and detection methods of KLKs. Furthermore, several specific members of KLKs were identified to be more significantly related to worse OS and DFS compared with other members.ConclusionThe present study demonstrated that KLKs may have the potential to serve as promising biomarkers to monitor CRC prognosis and progression. The promising results concerning the utility of KLKs in clinical practice encourage the further investigation of their clinical utility applicability as tumor markers of CRC.
Plasmodium vivax liver stage assay platforms using Indian clinical isolates
Authors: Subramani Pradeep A. , Vartak-Sharma Neha , Sreekumar Seetha , Mathur Pallavi , Nayer Bhavana , Dakhore Sushrut , Basavanna Sowmya K. , Kalappa Devaiah M. , Krishnamurthy Ramya V. , Mukhi Benudhar , Mishra Priyasha , Yoshida Noriko , Ghosh Susanta Kumar , Shandil Radhakrishan , Narayanan Shridhar , Campo Brice , Hasegawa Kouichi , Anvikar Anupkumar R. , Valecha Neena , Sundaramurthy Varadharajan 
Published: June 2020

Abstract
Background
Vivax malaria is associated with significant morbidity and economic loss, and constitutes the bulk of malaria cases in large parts of Asia and South America as well as recent case reports in Africa. The widespread prevalence of vivax is a challenge to global malaria elimination programmes. Vivax malaria control is particularly challenged by existence of dormant liver stage forms that are difficult to treat and are responsible for multiple relapses, growing drug resistance to the asexual blood stages and host-genetic factors that preclude use of specific drugs like primaquine capable of targeting Plasmodium vivax liver stages. Despite an obligatory liver-stage in the Plasmodium life cycle, both the difficulty in obtaining P. vivax sporozoites and the limited availability of robust host cell models permissive to P. vivax infection are responsible for the limited knowledge of hypnozoite formation biology and relapse mechanisms, as well as the limited capability to do drug screening. Although India accounts for about half of vivax malaria cases world-wide, very little is known about the vivax liver stage forms in the context of Indian clinical isolates.

Methods
To address this, methods were established to obtain infective P. vivax sporozoites from an endemic region in India and multiple assay platforms set up to detect and characterize vivax liver stage forms. Different hepatoma cell lines, including the widely used HCO4 cells, primary human hepatocytes as well as hepatocytes obtained from iPSC’s generated from vivax patients and healthy donors were tested for infectivity with P. vivax sporozoites.

Results
Both large and small forms of vivax liver stage are detected in these assays, although the infectivity obtained in these platforms are low.

Conclusions
This study provides a proof of concept for detecting liver stage P. vivax and provide the first characterization of P. vivax liver stage forms from an endemic region in India.
Self-perception of dietary quality and adherence to food groups dietary recommendations among Mexican adults
Authors: Batis Carolina , Castellanos-Gutiérrez Analí , Aburto Tania C. , Jiménez-Aguilar Alejandra , Rivera Juan A. , Ramírez-Silva Ivonne 
Published: June 2020

Abstract
Background
Mexicans’ adherence to food group’s dietary recommendations is low and an inaccurate self-perception of dietary quality might perpetuate this low adherence. Our aim was to compare the intake and the adherence to the dietary recommendations for several food groups, subgroups, and to an overall Mexican Diet Quality Index (MxDQI), among those that perceived their diet as healthy vs. those that did not.

Methods
We analyzed data from 989 subjects 20–59 y old from the nationally representative Mexican National Health and Nutrition Survey 2016. Dietary intake was collected with one 24-h recall and a repeated recall in 82 subjects. Self-perception of dietary quality was evaluated with the following question “Do you consider that your diet is healthy? (yes/no)”. We used the National Cancer Institute method to estimate the usual intake. We compared the mean intake adjusted by sociodemographic variables and the percentage of adherence according to the self-perception of dietary quality among the whole sample and in sociodemographic subpopulations.

Results
Sixty percent perceived their diet as healthy, and their adherence to recommendations was low [20% for fruits and vegetables, < 8% for legumes, seafood and SSBs, and ~ 50% for processed meats and high in saturated fat and/or added sugar (HSFAS) products]. The mean number of recommendations they met was 2.8 (out of 7) vs. 2.6 among the rest of the population (p > 0.05), and the MxDQI score was 40 vs. 37 (out of 100 points). The only food groups and subgroups with a statistically significant difference between those that perceived their diet as healthy vs. unhealthy were fruits [38 g/d (95% CI 3, 73)], fruit juices [27 g/d (95% CI 2, 52)], industrialized SSBs [− 35 kcal/d (− 70, − 1)] and salty snacks [− 40 kcal/d (− 79, − 1)]. Other differences were small or inconsistent across subgroups of the population.

Conclusions
Those that perceived their diet as healthy only had a slightly healthier diet than the rest of the population, moreover, their adherence to recommendations was very low. Hence, it is necessary to improve their nutrition knowledge.
Urban–rural disparity in the relationship between ambient air pollution and preterm birth
Authors: Li Long , Ma Jing , Cheng Yang , Feng Ling , Wang Shaoshuai , Yun Xiao , Tao Shu 
Published: June 2020

AbstractBackgroundSome studies have reported that air pollution exposure can have adverse effects on pregnancy outcomes. However, the disparity between urban and rural areas in the risk of preterm birth (PTB) has yet to be elucidated. Considering geographic contexts as homogeneous or ignoring urban–rural differences cannot accurately reveal the disparities in the health effects of air pollution under different geographic contexts. The aims of this study were to examine the disparities in the risks of PTB in three different regions and five urban–rural types and to investigate the extent to which fine particulate matter (PM2.5) exposure during the entire pregnancy can explain the variations.MethodsWe collected data on 429,865 singleton newborns born in 2014 in Hubei Province, China, and divided Hubei Province into three regions. Spatial correlation methods were employed to measure the associations between the rate of PTB and air pollution using average annual indexes for the entire province and regions. A series of multilevel logistic models were conducted to examine disparities in the risks of PTB with decreases in urbanity and the effects of air pollution exposure on the occurrence of preterm births.ResultsThe PM2.5concentration was significantly different across the regions. The eastern region had the most wide-ranged and serious level of pollution, whereas the levels in the middle and western regions weakened. The odds of PTB and air pollution exhibited a positive spatial correlation for the entire province and in the east (BiMoran’s I = 0.106 and 0.697, respectively). Significant urban–rural disparities in the risks of PTB were noted in the east and middle regions, and the mean PM2.5exposure during the entire pregnancy was positively associated with PTB risk. However, in the west, the results showed weak differences in the risks of PTB among the five urban–rural types and an insignificant effect of PM2.5exposure. The direction of the effect of district/county-level income on PTB varied by region.ConclusionsThis study finds that air pollution exposure and PTB have significant and positive spatial relationships in areas with a serious air pollution burden. The risks of PTB in three regions of Hubei Province follow the same W-shaped pattern as urbanity decreases and rurality increases. High levels of air pollution exposure may be an important disadvantage for urban pregnant women in this setting.
Association between fasting plasma glucose and nonalcoholic fatty liver disease in a nonobese Chinese population with normal blood lipid levels: a prospective cohort study
Authors: Zou Yang , Yu Meng , Sheng Guotai 
Published: June 2020

Abstract
Background
Fasting plasma glucose (FPG) is an easily quantifiable and inexpensive metabolic marker, which is often used to assess cardiovascular disease and diabetes. However, there have been limited studies on the association between FPG and nonalcoholic fatty liver disease (NAFLD) risk in nonobese people, especially in Chinese individuals. The purpose of this study was to investigate the association between FPG and NAFLD in nonobese Chinese people with normal blood lipid levels.

Methods
In this prospective cohort study, 9767 nonobese participants with normal blood lipid levels without NAFLD were recruited and prospectively followed for 5 years. The Cox proportional hazard model was used to evaluate the risk factors of NAFLD. Moreover, a Cox model with cubic spline functions and smooth curve fitting (the cubic spline smoothing) were used to identify the nonlinear association between FPG and NAFLD.

Results
During the 5-year follow-up, 841 (8.61%) participants were diagnosed with NAFLD. The good functional results (without NAFLD) estimated by the Kaplan-Meier method for 1 year, 2 years, 3 years, 4 years, and 5 years were 98.84, 95.35, 91.67%, 87.57 and 74.86%, respectively. Additionally, through the Cox proportional hazard model, after adjusting for other covariates, there was an independent positive correlation between FPG and increased NAFLD risk (HR:1.21, 95% CI:1.15–1.28, P < 0.0001), and the NAFLD risk was incrementally higher with the rising FPG quartile. The nonlinear association between FPG and NAFLD was visualized by cubic spline smoothing technique. It was calculated that the inflection point of FPG was 5.54. When FPG ≤ 5.54, there was a positive correlation between FPG and the risk of NAFLD (HR:2.20, 95% CI:1.78–2.73, P < 0.0001). When FPG > 5.54, the risk of NAFLD increased by 50% (HR:1.10, 95% CI:1.02–1.18, P = 0.0159) compared with the left side of the inflection point and gradually leveled off.

Conclusions
In a nonobese Chinese population with normal lipid levels, there is an independent nonlinear association between FPG and NAFLD, and the increase in FPG may indicate an increased risk of NAFLD. Additionally, this independent association is more obvious in the short stature population.
Translation, cultural adaptation and validation of the Chinese Multimorbidity Treatment Burden Questionnaire(C-MTBQ): a study of older hospital patients
Authors: Dou Liyuan , Huang Juan , Duncan Polly , Guo Lixiang 
Published: June 2020

Abstract
Background
Due to an ageing population, multimorbidity is becoming more common. Treatment burden (the effort required of patients to look after their health and the impact this has on their wellbeing) is prevalent in patients with multimorbidity. The Multimorbidity Treatment Burden Questionnaire (MTBQ) is a patient-reported outcome measure of treatment burden that has been validated amongst patients with multimorbidity in the UK. The aim of this study was to translate and culturally adapt the MTBQ into Chinese and to assess its reliability and validity in elderly patients with multimorbidity in hospital.

Methods
The original English version of the MTBQ was translated into Chinese using Brislin’s model of cross-culture translation. The C-MTBQ was piloted on a sample of 30 elderly patients with multimorbidity prior to being completed by 156 Chinese elderly patients with multimorbidity recruited from a hospital in Zhengzhou, China. We examined the proportion of missing data, the distribution of responses and floor and ceiling effects for each question. Factor analysis, Cronbach’s alpha, intraclass coefficient and Spearman’s rank correlations assessed dimensional structure, internal consistency reliability, test-retest reliability and criterion validity, respectively.

Results
The average age of the respondents was 73.5 years (range 60–99 years). The median C-MTBQ global score was 20.8 (interquartile range 12.5–29.2). Significant floor effects were seen for all items. Factor analysis supported a three-factor structure. The C-MTBQ had high internal consistency (Cronbach’s alpha coefficient, 0.76) and test-retest reliability (the intraclass correlation coefficient, 0.944), the correlations between every item and global scores scored > 0.4. The scale content validity index(S-CVI) was 0.89, and the item level content validity index(I-CVI)was 0.83 ~ 1.00. The criterion validity was 0.875.

Conclusion
The Chinese version of MTBQ showed satisfactory reliability and validity in elderly patients with multimorbidity, and could be used as a tool to measure treatment burden of elderly patients with multimorbidity in hospital.
Natural disease progression and novel survival prediction model for hepatocellular carcinoma with spinal metastases: a 10-year single-center study
Authors: Phinyo Phichayut , Boonyanaruthee Chonmavadh , Paholpak Permsak , Pruksakorn Dumneoensun , Phanphaisarn Areerak , Sangsin Apiruk 
Published: June 2020

Abstract
Background
Individual prediction of life expectancy in patients with spinal metastases from hepatocellular carcinoma (HCC) is key for optimal treatment selection, especially when identifying potential candidates for surgery. Most reported prognostic tools provide categorical predictions, and only a few include HCC-related factors. This study aimed to investigate the natural progression of the disease and develop a prognostic tool that is capable of providing individualized predictions.

Methods
Patients with HCC-derived metastatic spinal disease were identified from a retrospective cohort of patients with spinal metastases who were diagnosed at Chiang Mai University Hospital between 2006 and 2015. Kaplain–Meier methods and log-rank tests were used to statistically evaluate potential factors. Significant predictors from the univariable analysis were included in the flexible parametric survival regression for the development of a prognostic prediction model.

Results
Of the 1143 patients diagnosed with HCC, 69 (6%) had spinal metastases. The median survival time of patients with HCC after spinal metastases was 79 days. In the multivariable analysis, a total of 11 potential clinical predictors were included. After backward elimination, four final predictors remained: patients aged > 60 years, Karnofsky Performance Status, total bilirubin level, and multifocality of HCC. The model showed an acceptable discrimination at C-statistics 0.73 (95% confidence interval 0.68–0.79) and fair calibration.

Conclusion
Four clinical parameters were used in the development of the individual survival prediction model for patients with HCC-derived spinal metastases of Chiang Mai University or HCC-SM CMU model. Prospective external validation studies in a larger population are required prior to the clinical implication of the model.
Evaluation of M2-like macrophage enrichment after diffuse traumatic brain injury through transient interleukin-4 expression from engineered mesenchymal stromal cells
Authors: Enam Syed Faaiz , Kader Sajidur Rahman , Bodkin Nicholas , Lyon Johnathan G. , Calhoun Mark , Azrak Cesar , Tiwari Pooja Munnilal , Vanover Daryll , Wang Haichen , Santangelo Philip J. , Bellamkonda Ravi Venkat 
Published: June 2020

AbstractBackgroundAppropriately modulating inflammation after traumatic brain injury (TBI) may prevent disabilities for the millions of those inflicted annually. In TBI, cellular mediators of inflammation, including macrophages and microglia, possess a range of phenotypes relevant for an immunomodulatory therapeutic approach. It is thought that early phenotypic modulation of these cells will have a cascading healing effect. In fact, an anti-inflammatory, “M2-like” macrophage phenotype after TBI has been associated with neurogenesis, axonal regeneration, and improved white matter integrity (WMI). There already exist clinical trials seeking an M2-like bias through mesenchymal stem/stromal cells (MSCs). However, MSCs do not endogenously synthesize key signals that induce robust M2-like phenotypes such as interleukin-4 (IL-4).MethodsTo enrich M2-like macrophages in a clinically relevant manner, we augmented MSCs with synthetic IL-4 mRNA to transiently express IL-4. These IL-4 expressing MSCs (IL-4 MSCs) were characterized for expression and functionality and then delivered in a modified mouse TBI model of closed head injury. Groups were assessed for functional deficits and MR imaging. Brain tissue was analyzed through flow cytometry, multi-plex ELISA, qPCR, histology, and RNA sequencing.ResultsWe observed that IL-4 MSCs indeed induce a robust M2-like macrophage phenotype and promote anti-inflammatory gene expression after TBI. However, here we demonstrate that acute enrichment of M2-like macrophages did not translate to improved functional or histological outcomes, or improvements in WMI on MR imaging. To further understand whether dysfunctional pathways underlie the lack of therapeutic effect, we report transcriptomic analysis of injured and treated brains. Through this, we discovered that inflammation persists despite acute enrichment of M2-like macrophages in the brain.ConclusionThe results demonstrate that MSCs can be engineered to induce a stronger M2-like macrophage response in vivo. However, they also suggest that acute enrichment of only M2-like macrophages after diffuse TBI cannot orchestrate neurogenesis, axonal regeneration, or improve WMI. Here, we also discuss our modified TBI model and methods to assess severity, behavioral studies, and propose that IL-4 expressing MSCs may also have relevance in other cavitary diseases or in improving biomaterial integration into tissues.
Effect of toxic trace element detoxification, body fat reduction following four-week intake of the Wellnessup diet: a three-arm, randomized clinical trial
Authors: Jung Su-Jin , Kim Woo-Lim , Park Byung-Hyun , Lee Seung-Ok , Chae Soo-Wan 
Published: June 2020

Abstract
Background
Detox diet are known as a popular dieting strategies that helps toxins elimination and weight manage but there is very little clinical evidence. The Wellnessup diet (WD) used in the present study designed as a healthy meals based on organic plant based diets including various vegetables, fruits, whole grains, nuts and phytonutrients.

Methods
To evaluate the effects of 4 week intake of the WD on toxic trace element detoxification, body fat reduction, and safety parameters. Forty-five women with body mass index (BMI) of 23.5–30 kg/m2 were recruited. Thirty of them were assigned 1:1 to the test group (WD, 15 subjects) and control group 1 (calorie-restricted diet, CRD, 15 subjects) in a single blind and randomized, and the remaining 15 subjects were assigned to control group 2 (maintaining regular diet, MRD). The primary outcome were toxic trace element levels in hair (29 types of heavy metals), and the secondary outcomes were changes in anthropometric and urinary organic acids.

Results
The levels of four toxic trace elements in hair decreased in the WD group after the diet compared to before the diet. Ni, Rh, Sn, and Ga were significantly lower in the WD group than in the CRD or MRD group (p < 0.05). At the end of the trial, both WD and CRD groups had lower BMI, Waist Circumference(WC), Hip Circumference(HC) and WHR compared to the baseline values (p < 0.05). Compared to the WD group, the CRD group had a greater mean change (p < 0.05) from the baseline for weight loss (− 3.22 ± 0.48 kg vs − 1.88 ± 0.95 kg vs) and fat free mass (− 2.08 kg vs − 1.09 kg). The weight, BMI, body fat mass, fat free mass, WC, and HC of the CRD group were significantly decreased compared to the MRD (p < 0.05). No significant changes in any safety parameter were observed.

Conclusions
Use of WD might have several beneficial effects and safety such as body fat reduction and improving some the element detoxification through caloric restriction but did not reducing body fat mass more than calorie-restricted diet.

Trial registration
This study was registered at Clinical Research Information Service (CRIS) of Republic of Korea (KCT0003002).