bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of atheromatosis in the prediabetes stage: a cross-sectional investigation of the ILERVAS project
Authors: Sánchez Enric , Betriu Àngels , López-Cano Carolina , Hernández Marta , Fernández Elvira , Purroy Francisco , Bermúdez-López Marcelino , Farràs-Sallés Cristina , Barril Silvia , Pamplona Reinald , Rius Ferran , Hernández Cristina , Simó Rafael , Lecube Albert ,   the ILERVAS project collaborators, Barbé Ferran , Valdivielso José-Manuel , Arqué Glòria , González Jessica , Vena Ana , Miquel Eva , Ortega-Bravo Marta , Torres Gerard , Cambray Serafín , Portero-Otin Manuel , Jové Mariona , Martínez-Alonso Montserrat , Castro Eva , Godoy Pere 
Published: November 2019

Abstract
Background
Prediabetes has recently been associated with subclinical atheromatous disease in the middle-aged population. Our aim was to characterize atheromatous plaque burden by the number of affected territories and the total plaque area in the prediabetes stage.

Methods
Atheromatous plaque burden (quantity of plaques and total plaque area) was assessed in 12 territories from the carotid and femoral regions using ultrasonography in 6688 non-diabetic middle-aged subjects without cardiovascular disease. Prediabetes was defined by glycosylated hemoglobin (HbA1c) between 5.7 and 6.4% according to the American Diabetes Association guidelines.

Results
Prediabetes was diagnosed in 33.9% (n = 2269) of the ILERVAS participants. Subjects with prediabetes presented a higher prevalence of subclinical atheromatous disease than participants with HbA1c < 5.7% (70.4 vs. 67.5%, p = 0.017). In the population with prediabetes this was observed at the level of the carotid territory (p < 0.001), but not in the femoral arteries. Participants in the prediabetes stage also presented a significantly higher number of affected territories (2 [1;3] vs. 1 [0;3], p = 0.002), with a positive correlation between HbA1c levels and the number of affected territories (r = 0.068, p < 0.001). However, atheromatosis was only significantly (p = 0.016) magnified by prediabetes in those subjects with 3 or more cardiovascular risk factors. The multivariable logistic regression model showed that the well-established cardiovascular risk factors together with HbA1c were independently associated with the presence of atheromatous disease in participants with prediabetes. When males and females were analyzed separately, we found that only men with prediabetes presented both carotid and femoral atherosclerosis, as well as an increase of total plaque area in comparison with non-prediabetic subjects.

Conclusions
The prediabetes stage is accompanied by an increased subclinical atheromatous disease only in the presence of other cardiovascular risk factors. Prediabetes modulates the atherogenic effect of cardiovascular risk factors in terms of distribution and total plaque area in a sex-dependent manner.
Trial registration NCT03228459 (clinicaltrials.gov)
Explaining income-related inequalities in cardiovascular risk factors in Tunisian adults during the last decade: comparison of sensitivity analysis of logistic regression and Wagstaff decomposition analysis
Authors: Saidi Olfa , Zoghlami Nada , Bennett Kathleen E. , Mosquera Paola Andrea , Malouche Dhafer , Capewell Simon , Romdhane Habiba Ben , O’Flaherty Martin 
Published: November 2019

Abstract
Background
It is important to quantify inequality, explain the contribution of underlying social determinants and to provide evidence to guide health policy. The aim of the study is to explain the income-related inequalities in cardiovascular risk factors in the last decade among Tunisian adults aged between 35 and 70 years old.

Methods
We performed the analysis by applying two approaches and compared the results provided by the two methods. The methods were global sensitivity analysis (GSA) using logistic regression models and the Wagstaff decomposition analysis.

Results
Results provided by the two methods found a higher risk of cardiovascular diseases and diabetes in those with high socio-economic status in 2005. Similar results were observed in 2016.
In 2016, the GSA showed that education level occupied the first place on the explanatory list of factors explaining 36.1% of the adult social inequality in high cardiovascular risk, followed by the area of residence (26.2%) and income (15.1%). Based on the Wagstaff decomposition analysis, the area of residence occupied the first place and explained 40.3% followed by income and education level explaining 19.2 and 14.0% respectively. Thus, both methods found similar factors explaining inequalities (income, educational level and regional conditions) but with different rankings of importance.

Conclusions
The present study showed substantial income-related inequalities in cardiovascular risk factors and diabetes in Tunisia and provided explanations for this. Results based on two different methods similarly showed that structural disparities on income, educational level and regional conditions should be addressed in order to reduce inequalities.
Triglyceride to high-density lipoprotein cholesterol ratio is associated with increased mortality in older patients on peritoneal dialysis
Authors: Zhan Xiaojiang , Yang Mei , Zhou Ruitong , Wei Xin , Chen Yanbing , Chen Qinkai 
Published: November 2019

Abstract
Background
The triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) has been suggested as a simple method to identify unfavorable cardiovascular (CV) outcomes in the general population. The aim of this study was to investigate the association between the TG/HDL-C ratio and all-cause and CV mortality in peritoneal dialysis (PD) patients.

Methods
We retrospectively analyzed patients on PD from November 1, 2005, to February 28, 2017, with a follow-up period lasting until May 31, 2017. The main outcomes were all-cause and CV mortality.

Results
Among the 973 PD patients, the mean age was 49.67 ± 14.58 (y). During a median follow-up period of 27.2 months (IQR = 13.4–41.5 months), 229 (23.5%) patients died, with 120 (12.3%) dying as a result of CV diseases. The median serum TG/HDL-C ratio was 1.11 (IQR = 0.71–1.80). In a multivariate Cox regression analysis, patients with higher TG/HDL-C ratio levels (tertile 3) had a higher incidence of CV mortality (adjusted HR = 2.12; 95% CI: 1.21–3.72; P = 0.009) and all-cause mortality (adjusted HR = 2.08; 95% CI: 1.37–3.14; P = 0.001) compared to patients in tertile 1. These associations persisted after excluding the patients who have already taken lipid-lowering medications. For older patients (> 60 years), each 1-unit higher baseline TG/HDL-C level was associated with a 48% (95% CI: 1.06–2.07; P = 0.021) increased risk of all-cause mortality and a 59% (95% CI: 1.03–2.45; P = 0.038) increased risk of CV mortality; however, this association was not observed in patients ≤60 years of age.

Conclusions
A higher serum TG/HDL-C ratio was an independent predictor of all-cause and CV mortality in PD patients. Furthermore, an elevated TG/HDL-C ratio was significantly associated with higher all-cause and CV mortality in older PD patients.
Myocardial tissue characterisation using echocardiographic deformation imaging
Authors: Moharram Mohammed A. , Lamberts Regis R. , Whalley Gillian , Williams Michael J. A. , Coffey Sean 
Published: November 2019

AbstractMyocardial pathology results in significant morbidity and mortality, whether due to primary cardiomyopathic processes or secondary to other conditions such as ischemic heart disease. Cardiac imaging techniques characterise the underlying tissue directly, by assessing a signal from the tissue itself, or indirectly, by inferring tissue characteristics from global or regional function. Cardiac magnetic resonance imaging is currently the most investigated imaging modality for tissue characterisation, but, due to its accessibility, advanced echocardiography represents an attractive alternative. Speckle tracking echocardiography (STE) is a reproducible technique used to assess myocardial deformation at both segmental and global levels. Since distinct myocardial pathologies affect deformation differently, information about the underlying tissue can be inferred by STE. In this review, the current available studies correlating STE deformation parameters with underlying tissue characteristics in humans are examined, with separate emphasis on global and segmental analysis. The current knowledge is placed in the context of integrated backscatter and the future of echocardiographic based tissue characterisation is discussed. The use of these imaging techniques to more precisely phenotype myocardial pathology more precisely will allow the design of translational cardiac research studies and, potentially, tailored management strategies.
Idelalisib addition has neutral to beneficial effects on quality of life in bendamustine/rituximab-treated patients: results of a phase 3, randomized, controlled trial
Authors: Montillo Marco , Illés Árpád , Robak Tadeusz , Pristupa Alexander S. , Wach Malgorzata , Egyed Miklós , Delgado Julio , Jurczak Wojciech , Morschhauser Franck , Schuh Anna , Eradat Herbert , Shreay Sanatan , Barrientos Jacqueline C. , Zelenetz Andrew D. 
Published: November 2019

Abstract
Background
In a phase 3 randomized, double-blind, placebo-controlled trial, treatment with idelalisib, a phosphoinositol-3 kinase δ inhibitor, + bendamustine/rituximab improved progression-free survival (PFS) and overall survival (OS) in adult patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL). Here we report the results of health-related quality of life (HRQL) analyses from this study.

Methods
From June 15, 2012 to August 21, 2014, 416 patients with R/R CLL were enrolled; 207 patients were randomized to the idelalisib arm and 209 to the placebo arm. In the 416 patients randomized to receive bendamustine/rituximab and either oral idelalisib 150 mg twice-daily or placebo, HRQL was assessed at baseline and throughout the blinded part of the study using the Functional Assessment of Cancer Therapy–Leukemia (FACT-Leu) and EuroQoL Five-Dimension (EQ-5D) visual analogue scale (VAS) questionnaires. The assessments were performed at scheduled patient visits; every 4 weeks for the first 6 months from the initiation of treatment, then every 8 weeks for the next 6 months, and every 12 weeks thereafter until end of study. Least-squares mean changes from baseline were estimated using a mixed-effects model by including treatment, time, and treatment-by-time interaction, and stratification factors as fixed effects. Time to first symptom improvement was assessed by Kaplan-Meier analysis.

Results
In mixed-effects model analysis, idelalisib + bendamustine/rituximab treatment led to clinically meaningful improvements from baseline in leukemia-associated symptoms. Moreover, per Kaplan-Meier analysis, the proportion of patients with symptom improvement was higher and time to improvement was shorter among patients in the idelalisib-containing arm compared with those who did not receive idelalisib. The physical and social/family FACT-Leu subscale scores, along with the self-rated health assessed by EQ-VAS, showed improvement with idelalisib over placebo, but the difference did not reach statistical significance. The functional and emotional FACT-Leu subscale scores remained similar to placebo.

Conclusions
Addition of idelalisib to bendamustine/rituximab, apart from improving PFS and OS, had a neutral to beneficial impact on HRQL in patients with R/R CLL, particularly by reducing leukemia-specific disease symptoms.

Trial registration
Clinicaltrials.gov NCT01569295. Registered April 3, 2012.
Psychological wellbeing in a resource-limited work environment: examining levels and determinants among health workers in rural Malawi
Authors: Lohmann Julia , Shulenbayev Olzhas , Wilhelm Danielle , Muula Adamson S. , De Allegri Manuela 
Published: November 2019

Abstract
Background
A competent, responsive, and productive health workforce is central to a well-performing health system capable of providing universal access to high-quality care. Ensuring health workers’ psychological wellbeing is critical to sustaining their availability and productivity. This is particularly true in heavily constrained health systems in low- and lower-middle-income countries. Research on the issue, however, is scarce. This study aimed to contribute to filling the gap in knowledge by investigating levels of and factors associated with psychological wellbeing of mid-level health workers in Malawi.

Methods
The study relied on a cross-sectional sample of 174 health workers from 33 primary- and secondary-level health facilities in four districts of Malawi. Psychological wellbeing was measured using the WHO-5 Wellbeing Index. Data were analyzed using linear and logistic regression models.

Results
Twenty-five percent of respondents had WHO-5 scores indicative of poor psychological wellbeing. Analyses of factors related to psychological wellbeing showed no association with sex, cadre, having dependents, supervision, perceived coworker support, satisfaction with the physical work environment, satisfaction with remuneration, and motivation; a positive association with respondents’ satisfaction with interpersonal relationships at work; and a negative association with having received professional training recently. Results were inconclusive in regard to personal relationship status, seniority and responsibility at the health facility, clinical knowledge, perceived competence, perceived supervisor support, satisfaction with job demands, health facility level, data collection year, and exposure to performance-based financing.

Conclusions
The high proportion of health workers with poor wellbeing scores is concerning in light of the general health workforce shortage in Malawi and strong links between wellbeing and work performance. While more research is needed to draw conclusions and provide recommendations as to how to enhance wellbeing, our results underline the importance of considering this as a key concern for human resources for health.
Atheroprotective effects of methotrexate via the inhibition of YAP/TAZ under disturbed flow
Authors: Liu Dandan , Lv Hang , Liu Qi , Sun Yanli , Hou Shenglong , Zhang Lu , Yang Mengyue , Han Baihe , wang Gang , Wang Xuedong , Du Wenjuan , Nie Honggang , Zhang Ruoxi , Huang Xingtao , Hou Jingbo , Yu Bo 
Published: November 2019

Abstract
Background
Atherosclerosis preferentially develops in regions of disturbed flow (DF). Emerging evidence indicates that yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), which are both effectors of the Hippo pathway, sense different blood flow patterns and regulate atherosclerotic lesions. We previously found that methotrexate (MTX) reduces in-stent neoatherosclerosis, decreases the plaque burden, and has an effect on local fluid shear stress. Here, we investigated the atheroprotective effect of MTX under DF and the mechanisms underlying these properties.

Methods
Human umbilical vein endothelial cells (HUVECs) were subjected to biomechanical stretch using a parallel-plate flow system and treated with or without MTX at therapeutically relevant concentrations. Additionally, an extravascular device was used to induce DF in the left common carotid artery of C57BL/6 mice, followed by treatment with MTX or 0.9% saline. The artery was then assessed histopathologically after 4 weeks on a Western diet.

Results
We observed that MTX significantly inhibited DF-induced endothelial YAP/TAZ activation. Furthermore, it markedly decreased pro-inflammatory factor secretion and monocyte adhesion in HUVECs but had no effect on apoptosis. Mechanistically, AMPKa1 depletion attenuated these effects of MTX. Accordingly, MTX decreased DF-induced plaque formation, which was accompanied by YAP/TAZ downregulation in vivo.

Conclusions
Taken together, we conclude that MTX exerts protective effects via the AMP-dependent kinase (AMPK)-YAP/TAZ pathway. These results provide a basis for the prevention and treatment of atherosclerosis via the inhibition of YAP/TAZ.
Profiling the microRNA signature of the peripheral sensory ganglia in experimental autoimmune encephalomyelitis (EAE)
Authors: Friedman Timothy N. , Yousuf Muhammad Saad , Catuneanu Ana , Desai Mansi , Juźwik Camille A. , Fournier Alyson E. , Kerr Bradley J. 
Published: November 2019

AbstractBackgroundMultiple sclerosis is an autoimmune disease with a distinct female bias, as well as a high prevalence of neuropathic pain in both sexes. The dorsal root ganglia (DRG) contain the primary sensory neurons that give rise to pain, and damage to these neurons may lead to neuropathic pain. Here, we investigate the sex differences of the DRG transcriptome in a mouse model of MS.MethodsNext-generation sequencing was used to establish RNA and microRNA profiles from the DRG of mice with MOG35–55-induced EAE, a model of CNS inflammation that mimics aspects of MS. Differential expression and multiple meta-analytic approaches were used to compare expression profiles in immunized female and male mice. Differential expression of relevant genes and microRNAs were confirmed by qPCR.ResultsThree thousand five hundred twenty genes and 29 microRNAs were differentially expressed in the DRG of female mice with MOG35–55-EAE, while only 189 genes and 3 microRNAs were differentially expressed in males with MOG35–55-EAE. Genes related to the immune system were uniquely regulated in immunized female mice. Direct comparison of sex within disease indicates significant differences in interferon and phagosomal pathways between the sexes. miR-21a-5p is the primary dysregulated microRNA in both sexes, with females having additional dysregulated microRNAs, including miR-122-5p.ConclusionsThis study provides evidence that females are uniquely affected by MOG35–55-EAE and that this difference may result from additional signaling not present in the male. The altered transcriptome of females correlates with other studies finding hyperactivity of pain-sensing neurons and suggests underlying sex-specific pathways for neuropathic pain.
Anti-neuroinflammation ameliorates systemic inflammation-induced mitochondrial DNA impairment in the nucleus of the solitary tract and cardiovascular reflex dysfunction
Authors: Fu Mu-Hui , Chen I-Chun , Lee Chou-Hwei , Wu Chih-Wei , Lee Yu-Chi , Kung Yu Chih , Hung Chun-Ying , Wu Kay L. H. 
Published: November 2019

AbstractBackgroundDecreased heart rate variability (HRV) leads to cardiovascular diseases and increased mortality in clinical studies. However, the underlying mechanisms are still inconclusive. Systemic inflammation-induced neuroinflammation is known to impair the autonomic center of cardiovascular regulation. The dynamic stability of blood pressure and heart rate (HR) is regulated by modulation of the reciprocal responses of sympathetic and parasympathetic tone by the baroreflex, which is controlled by the nucleus of the solitary tract (NTS).MethodsSystemic inflammation was induced byE. colilipopolysaccharide (LPS, 1.2 mg/kg/day, 7 days) peritoneal infusion via an osmotic minipump in normotensive Sprague-Dawley rats. Systolic blood pressure (SBP) and HR were measured by femoral artery cannulation and recorded on a polygraph under anesthesia. The low-frequency (LF; 0.25–0.8 Hz) and high-frequency (HF; 0.8–2.4 Hz) components of SBP were adopted as the indices for sympathetic vasomotor tone and parasympathetic vasomotor tone, while the baroreflex effectiveness index (BEI) was adopted from the analysis of SBP and pulse interval (PI). The plasma levels of proinflammatory cytokines and mitochondrial DNA (mtDNA) oxidative damage were analyzed by ELISA. Protein expression was evaluated by Western blot. The distribution of oxidative mtDNA was probed by immunofluorescence. Pharmacological agents were delivered via infusion into the cisterna magna with an osmotic minipump.ResultsThe suppression of baroreflex sensitivity was concurrent with increased SBP and decreased HR. Neuroinflammatory factors, including TNF-α, CD11b, and Iba-1, were detected in the NTS of the LPS group. Moreover, indices of mtDNA damage, including 8-OHdG and γ-H2AX, were significantly increased in neuronal mitochondria. Pentoxifylline or minocycline intracisternal (IC) infusion effectively prevented mtDNA damage, suggesting that cytokine and microglial activation contributed to mtDNA damage. Synchronically, baroreflex sensitivity was effectively protected, and the elevated blood pressure was significantly relieved. In addition, the mtDNA repair mechanism was significantly enhanced by pentoxifylline or minocycline.ConclusionThese results suggest that neuronal mtDNA damage in the NTS induced by neuroinflammation could be the core factor in deteriorating baroreflex desensitization and subsequent cardiovascular dysfunction. Therefore, the enhancement of base excision repair (BER) signaling in mitochondria could be a potential therapeutic strategy for cardiovascular reflex dysregulation.
Impact of internal female migration on unmet need for modern contraception in Zambia
Authors: Almonte Melanie T. , Lynch Caroline A. 
Published: November 2019

AbstractBackgroundUnmet need for contraception, the proportion of women who want to limit or delay childbirth but use no form of contraception, is the core indicator to evaluate the effectiveness of family planning programs. Understanding how migration influences unmet need is important to identify to whom and how to target sexual and reproductive health programs. We assessed how migration status in rural and urban settings is associated with having an unmet need for family planning.MethodsData on sexually active, fecund, reproductive-aged (15–49 years) women from the 2013–14 Zambia Demographic and Health Survey were analysed through univariate and multivariate logistic regression models.ResultsUnmet need for modern contraceptive methods was significantly higher among rural to rural migrant women (OR 1.30, 95%CI 1.00–1.70p < 0.05) and rural non-migrant women (OR 1.41, 95%CI 1.06–1.85p < 0.01) compared to urban non-migrant women after controlling for age, marital status, parity, religion, education and wealth.ConclusionWomen residing in, and migrating between, rural areas were significantly more likely to have an unmet need for contraception. Our findings highlight the importance of understanding migration and migrant streams to strengthen family planning programs. In Zambia, a focus on rural-rural migrants, rural non-migrants and the poorest could improve the health of the entire population.