bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microvascular complications burden (nephropathy, retinopathy and peripheral polyneuropathy) affects risk of major vascular events and all-cause mortality in type 1 diabetes: a 10-year follow-up study
Authors: Garofolo Monia , Gualdani Elisa , Giannarelli Rosa , Aragona Michele , Campi Fabrizio , Lucchesi Daniela , Daniele Giuseppe , Miccoli Roberto , Francesconi Paolo , Del Prato Stefano , Penno Giuseppe 
Published: November 2019

AbstractBackgroundMicrovascular complications (MC) have been claimed to increase the risk for cardiovascular disease in diabetic subjects. However, the effect of MC burden on the risk of major vascular outcomes and all-cause mortality in type 1 diabetes is still poorly explored. We evaluated the relationship between microvascular complications burden and incidence of major cardiovascular events and all-cause mortality in subjects with type 1 diabetes.MethodsWe recruited 774 participants with type 1 diabetes in a single-center observational study over a follow-up of 10.8 ± 2.5 years. Hazard ratios (HR) for cardiovascular outcomes and all-cause death associated with microvascular complications were determined by unadjusted and adjusted Cox regression analysis.ResultsOut of 774 individuals, 54.9% had no-MC, 32.3% 1 MC, 9.7% 2 MC and 3.1% 3 MC. A total of 54 deaths (7.0%) occurred. Death rate increased from no-MC 2.1% (Ref) to 1 MC 7.2% (HR 3.54 [95% CI 1.59–7.87]), 2 MC 14.7% (HR 6.41 [95% CI 2.65–15.49]) and 3 MC 66.7% (HR 41.73 [95% CI 18.42–94.57], p < 0.0001). After adjustments, HRs were: 1 MC 2.05 (95% CI 0.88–4.76), 2 MC 1.98 (95% CI 0.75–5.21), 3 MC 7.02 (95% CI 2.44–20.20, p = 0.002). Forty-nine subjects (6.7%) had at least one cardiovascular event, and cumulative incidence went from no-MC 2.2% (Ref) to 1 MC 5.0%; (HR 2.27 [95% CI 0.96–5.38]), 2 MC 26.8% (HR 12.88 [95% CI 5.82–28.50]) and 3 MC 40.9% (HR 29.34 [95% CI 11.59–74.25], p < 0.0001). Upon adjustments, HRs were: 1 MC 1.59 (95% CI 0.65–3.88), 2 MC 4.33 (95% CI 1.75–10.74), 3 MC 9.31 (95% CI 3.18–27.25, p < 0.0001). Thirty-five individuals (4.8%) had at least one coronary event, which cumulative incidence increased with MC burden (p < 0.0001).ConclusionsIn type 1 diabetes, microvascular complications burden increases in an independent dose-dependent manner the risk of major cardiovascular outcomes and all-cause mortality. The presence and number of microvascular complications should be considered in stratifying overall cardiovascular risk in type 1 diabetes.
Differences in lipid metabolism between anagliptin and sitagliptin in patients with type 2 diabetes on statin therapy: a secondary analysis of the REASON trial
Authors: Chihara Atsuko , Tanaka Atsushi , Morimoto Takeshi , Sakuma Mio , Shimabukuro Michio , Nomiyama Takashi , Arasaki Osamu , Ueda Shinichiro , Node Koichi 
Published: November 2019

Abstract
Background
Anagliptin, a dipeptidyl peptidase-4 inhibitor, is reported to reduce the level of low-density lipoprotein cholesterol (LDL-C). The underlying mechanism of this effect and effect on lipid metabolism however remains uncertain.

Aim and methods
We therefore evaluate the effects of anagliptin on lipid metabolism-related markers compared with those of sitagliptin. The study was a secondary analysis using data obtained from the Randomized Evaluation of Anagliptin versus Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial. This trial in patients with type 2 diabetes at a high risk of cardiovascular events and on statin therapy showed that anagliptin reduced LDL-C levels to a greater extent than sitagliptin. Cholesterol absorption (campesterol and sitosterol) and synthesis (lathosterol) markers were measured at baseline and 52 weeks in the study cohort (n = 353).

Results
There was no significant difference in the changes of campesterol or sitosterol between the two treatment groups (p = 0.85 and 0.55, respectively). Lathosterol concentration was increased significantly at 52 weeks with sitagliptin treatment (baseline, 1.2 ± 0.7 μg/mL vs. 52 weeks, 1.4 ± 1.0 μg/mL, p = 0.02), whereas it did not change in the anagliptin group (baseline, 1.3 ± 0.8 μg/mL vs. 52 weeks, 1.3 ± 0.7 μg/mL, p = 0.99). The difference in absolute change between the two groups showed a borderline significance (p = 0.06).

Conclusion
These findings suggest that anagliptin reduces LDL-C level by suppressing excess cholesterol synthesis, even in combination with statin therapy.
Trial registration ClinicalTrials.gov number NCT02330406. https://clinicaltrials.gov/ct2/show/NCT02330406; registered January 5, 2015.
MicroRNA-140-5p inhibits salivary adenoid cystic carcinoma progression and metastasis via targeting survivin
Authors: Qiao Zhu , Zou Yue , Zhao Hu 
Published: November 2019

Abstract
Background
Salivary adenoid cystic carcinoma (SACC) is one of the most frequent carcinomas derived from the salivary gland. Growing evidence implied the involvement of microRNAs (miRNAs) in SACC progression and metastasis. This study aimed to determine the regulatory role of miR-140-5p in SACC progression and metastasis and to explore the underlying mechanisms.

Materials and methods
MiR-140-5p and survivin mRNA expression levels were determined by quantitative real-time PCR; protein levels were evaluated by western blot assay; cell proliferation, growth, invasion, apoptosis and caspase-3 activity were evaluated by respective in vitro functional assays; xenograft nude mice model was used to assess the in vivo tumor growth; a luciferase reporter assay determined the interaction between miR-140-5p and survivin.

Results
MiR-140-5p overexpression suppressed SACC cell proliferation and invasion, induced cell apoptosis and inhibited in vivo tumor growth of SACC cells. The loss-of-function studies showed that miR-140-5p knockdown enhanced SACC cell proliferation and invasion, inhibited cell apoptosis and led to an accelerated in vivo tumor growth. The bioinformatics prediction and luciferase reporter assay revealed that miR-140-5p directly targeted survivin 3′ untranslated region, and survivin was inversely regulated by miR-140-5p. Knockdown of survivin exerted tumor-suppressive effects on SACC cells, while enforced expression of survivin counteracted the tumor-suppressive actions of miR-140-5p overexpression in SACC cells. Mechanistically, miR-140-5p modulated the protein expression levels of apoptosis- and epithelial-mesenchymal transition-related mediators as well as matrix metallopeptidase-2/-9 via targeting survivin. More importantly, the down-regulation of miR-140-5p and the up-regulation of survivin were detected in the SACC clinical tissues, and miR-140-5 expression was inversely correlated with survivin mRNA expression level in SACC tissues.

Conclusion
Our data indicated that miR-140-5p suppressed SACC cell proliferation and invasion, induced cell apoptosis via regulating survivin expression. The present study provide evidence that that miR-140-5p could be a promising target for treating SACC, which requires further investigations.
Gender difference in the association of dietary patterns and metabolic parameters with obesity in young and middle-aged adults with dyslipidemia and abnormal fasting plasma glucose in Taiwan
Authors: Lin Li-Yin , Hsu Chien-Yeh , Lee Hsiu-An , Tinkov Alexey A. , Skalny Anatoly V. , Wang Wan-Hsiang , Chao Jane C.-J. 
Published: November 2019

AbstractBackgroundThe increasing prevalence of obesity has become a pandemic problem, and dietary patterns are one of the important factors causing obesity. Although the correlation between dietary patterns and obesity has been well explored, the gender difference on the association between dietary patterns and obesity remains unclear. The objective of this study examined whether gender difference existed in the relationship of dietary patterns with metabolic parameters and specific indices of adiposity among young and middle-aged adults with dyslipidemia and abnormal fasting plasma glucose (FPG) in Taiwan.MethodsA total of 14,087 subjects aged between 20 and 50 years with dyslipidemia and abnormal FPG were recruited in Taiwan between 2001 and 2010 for a cross-sectional study. Dyslipidemia was defined primarily according to the National Cholesterol Education Program Adult Treatment Panel III guidelines with minor modification. Abnormal FPG level was defined by the American Diabetes Association. Principal component analysis was conducted to identify dietary patterns. Multivariate logistic regression analysis was performed to evaluate the association of dietary patterns and metabolic parameters with different indices of adiposity including general obesity, central obesity, and high body fat, stratified by gender.ResultsTwo dietary patterns derived from principal component analysis were the prudent dietary pattern and the western dietary pattern. Both men and women in the highest quartile of the western dietary pattern had a significantly increased odds ratio of general obesity, central obesity, and high body fat. However, only male subjects in the higher quartiles of the prudent dietary pattern had a significantly decreased odds ratio of all indices of obesity. Both men and women with higher high-density lipoprotein cholesterol and total cholesterol levels had a significantly reduced odds ratio of general and central obesity, while those with higher triglycerides and FPG levels had a significantly increased odds ratio of general and central obesity. Higher low-density lipoprotein cholesterol level was significantly associated with an elevated odds ratio of high body fat, while higher total cholesterol level was significantly correlated with a reduced odds ratio of high body fat only in women.ConclusionsGender difference exists in the association of dietary patterns and metabolic parameters with obesity and body fat in young and middle-aged adults with dyslipidemia and abnormal FPG in Taiwan.
Chemerin-induced macrophages pyroptosis in fetal brain tissue leads to cognitive disorder in offspring of diabetic dams
Authors: Liang Zhaoxia , Han Luyang , Sun Dianjianyi , Chen Yanmin , Wu Qi , Zhang Lixia , Zhou Menglin , Chen Danqing 
Published: November 2019

AbstractBackgroundChemerin is highly expressed in the serum, placenta tissue, and umbilical cord blood of diabetic mother; however, the impact of chemerin on cognitive disorders of offspring from mothers with diabetes in pregnancy remains unclear.MethodsA diabetic phenotype in pregnant mice dams was induced by streptozocin (STZ) injection or intraperitoneal injection of chemerin. Behavioral changes in offspring of diabetic dams and nondiabetic controls were assessed, and changes in chemerin, two receptors of chemerin [chemerin receptor 23 (ChemR23) and chemokine (C-C motif) receptor-like 2 (CCRL2)], macrophages, and neurons in the brain tissue were studied to reveal the underlying mechanism of the behavioral changes.ResultsChemerin treatment mimicked the STZ-induced symptom of maternal diabetes in mice along with the altered behavior of offspring in the open field test (OFT) assay. In the exploring process for potential mechanism, the brain tissues of offspring from chemerin-treated dams were observed with an increase level of macrophage infiltration and a decrease number of neuron cells. Moreover, an increased level of NOD-like receptor family pyrin domain containing 3 (NLRP3) and apoptosis-associated speck-like (Asc) protein as well as pyroptosis [characterized by increased active caspase-1 content and secretion of cytokines such as interleukin (IL) 1 beta (IL-1β) and IL-18] more activated in macrophages is also observed in the brain of these diabetic dam’s offspring, in the presence of ChemR23. In vitro, it was found that pyroptosis activation was increased in macrophages separated from the abdominal cavity of normal mice, after chemerin treatment. However, depletion of CCRL2 decreased the level of chemerin in the brain tissues of diabetic dams’ offspring; depletion of ChemR23 decreased macrophage pyroptosis, and depletion of either receptor reversed chemerin-mediated neurodevelopmental deficits and cognitive impairment of offspring of diabetic pregnant dams.ConclusionsChemerin induced diabetic pregnant disease and CCRL2 were required to enrich chemerin in the brain of offspring. Aggregation of chemerin could lead to macrophage recruitment, activation of pyroptosis, the release of inflammatory cytokines, a decrease in the number of neurons, and cognitive impairment in offspring in a ChemR23-dependent manner. Targeting CCRL2 and/or ChemR23 could be useful for treating neuropsychological deficits in offspring of dams with diabetes in pregnancy.
Natalizumab promotes activation and pro-inflammatory differentiation of peripheral B cells in multiple sclerosis patients
Authors: Traub Jan W. , Pellkofer Hannah L. , Grondey Katja , Seeger Ira , Rowold Christoph , Brück Wolfgang , Husseini Leila , Häusser-Kinzel Silke , Weber Martin S. 
Published: November 2019

Abstract
Background
In the past, multiple sclerosis (MS) medications have been primarily designed to modulate T cell properties. Based on the emerging concept that B cells are equally important for the propagation of MS, we compared the effect of four commonly used, primarily T cell-targeting MS medications on B cells.

Methods
Using flow cytometry, we analyzed peripheral blood mononuclear cells (PBMC) of untreated (n = 19) and dimethyl fumarate (DMF; n = 21)-, fingolimod (FTY; n = 17)-, glatiramer acetate (GA; n = 18)-, and natalizumab (NAT; n = 20)-treated MS patients, focusing on B cell maturation, differentiation, and cytokine production.

Results
While GA exerted minor effects on the investigated B cell properties, DMF and FTY robustly inhibited pro-inflammatory B cell function. In contrast, NAT treatment enhanced B cell differentiation, activation, and pro-inflammatory cytokine production when compared to both intraindividual samples collected before NAT treatment initiation as well as untreated MS controls. Our mechanistic in vitro studies confirm this observation.

Conclusion
Our data indicate that common MS medications have differential, in part opposing effects on B cells. The observed activation of peripheral B cells upon NAT treatment may be instructive to interpret its unfavorable effect in certain B cell-mediated inflammatory conditions and to elucidate the immunological basis of MS relapses after NAT withdrawal.

Trial registration
Protocols were approved by the ethical review committee of the University Medical Center Göttingen (#3/4/14).
The long-term outcomes of a cohort of adolescents and adults from Greece with autism spectrum disorder
Authors: Sevaslidou Isaia , Chatzidimitriou Christina , Abatzoglou Grigoris 
Published: November 2019

Abstract
Background
Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Although it is a lifelong condition, treatments and services can improve a person’s symptoms and ability to function. Research on the outcomes in adolescence and adult life and on the associated factors is limited. The objective of the present study is to examine the outcomes as well as the contributing factors in adolescents and adults diagnosed with ASD in Greece.

Method
Participants included 69 parents of individuals diagnosed with ASD in their childhood. Interviews were conducted with the parents, and archived medical and psychological records were collected. Participants had been diagnosed in the Child and Adolescent Unit of the 3d Psychiatric Clinic of the AHEPA Hospital in Thessaloniki, Greece between 1990 and 2007.

Results
The overall outcome was poor in most of cases (22.6% “very poor” and 24.5% “poor”); however, a substantial number had “good” (18.9%) or “very good” (22.6%) outcomes. Severity of initial diagnosis (χ2 = 65.956, DF = 8, p < 0.001), presence of comorbid disorders in childhood (χ2 = 14,085, DF = 4, p < 0.007), current comorbidity (χ2 = 15.834, DF = 4, p = 0.003), and certain developmental milestones [early acquisition of language skills (χ2 = 16.991, DF = 8, p = 0.030)] were positively correlated with adult outcomes.

Conclusions
Overall outcomes in the Greek sample were consistent with international studies. It seems that important contributing factors are comorbidity and especially overall lower cognitive function (intellectual disability), but further research is needed as well as enhanced adult-oriented research and intervention programs.
Teen Mental Health First Aid for years 7–9: a description of the program and an initial evaluation
Authors: Hart Laura M. , Bond Kathy S. , Morgan Amy J. , Rossetto Alyssia , Cottrill Fairlie A. , Kelly Claire M. , Jorm Anthony F. 
Published: November 2019

Abstract
Background
A teen Mental Health First Aid training course for high school students in years 10–12 (tMHFA 10–12) has previously been evaluated in uncontrolled and randomized controlled trials and found to improve Mental Health First Aid intentions, mental health literacy and to reduce stigma. This 3 × 75-min course has more recently been adapted for younger students in years 7–9 (tMHFA 7–9). The present study reports an initial uncontrolled trial of this new training course which aimed to assess feasibility and acceptability of the course and test effects on knowledge, attitudes and behaviour.

Methods
An uncontrolled trial was carried out in five schools with measures taken at pre-test, post-test and 3-month follow-up. The outcomes measured were: quality of first aid intentions to help peers, confidence in helping, stigmatising attitudes, recognition of anxiety disorder, number of adults thought to be helpful, help-seeking intentions, quality of support provided to a peer, quality of support received, and psychological distress. Questions were also asked about satisfaction with the course.

Results
There were 475 students (mean age 13.86 years) who provided data at baseline, with 76% of these providing data at post-test and 75% at follow-up. Sustained changes at follow-up were found for: number of adults thought to be helpful, some components of stigma, recognition of anxiety disorder, and quality of support provided to a peer. However, there was an unexpected decline in willingness to tell others about a mental health problem. Most students found the information presented to be new, easy to understand, and useful.

Conclusions
The tMHFA 7–9 training course produced some positive changes that were sustained over 3 months. However, the changes were not as strong as previously found for older high school students, suggesting the need for further refinement of the course.
Intersectoral collaboration for people-centred mental health care in Timor-Leste: a mixed-methods study using qualitative and social network analysis
Authors: Hall Teresa , Kakuma Ritsuko , Palmer Lisa , Minas Harry , Martins João , Armstrong Greg 
Published: November 2019

AbstractBackgroundIntersectoral collaboration is fundamental to the provision of people-centred mental health care, yet there is a dearth of research about how this strategy operates within mental health systems in low- and middle-income countries. This is problematic given the known attitudinal, structural and resource barriers to intersectoral collaboration in high-income country mental health systems. This study was conducted to investigate intersectoral collaboration for people-centred mental health care in Timor-Leste, a South-East Asian country in the process of strengthening its mental health system.MethodsThis study employed a mixed-methods convergent design. Qualitative data elicited from in-depth interviews with 85 key stakeholders and document review were complemented with quantitative social network analysis to assess understandings of, the strength and structure of intersectoral collaboration in the Timorese mental health system.ResultsThere was consensus among stakeholder groups that intersectoral collaboration for mental health is important in Timor-Leste. Despite resource restrictions discussed by participants, interview data and social network analysis revealed evidence of information and resource sharing among organisations working within the health and social (disability and violence support) sectors in Timor-Leste (network density = 0.55 and 0.30 for information and resource sharing, respectively). Contrary to the assumption that mental health services and system strengthening are led by the Ministry of Health, the mixed-methods data sources identified a split in stewardship for mental health between subnetworks in the health and social sectors (network degree centralisation = 0.28 and 0.47 for information and resource sharing, respectively).ConclusionsOverall, the findings suggest that there may be opportunities for intersectoral collaborations in mental health systems in LMICs which do not exist in settings with more formalised mental health systems such as HICs. Holistic understandings of health and wellbeing, and a commitment to working together in the face of resource restrictions suggest that intersectoral collaboration can be employed to achieve people-centred mental health care in Timor-Leste.
The use of lytic polysaccharide monooxygenases in anaerobic digestion of lignocellulosic materials
Authors: Costa Thales H. F. , Eijsink Vincent G. H. , Horn Svein Jarle 
Published: November 2019

AbstractBackgroundThe recent discovery that LPMOs can work under anaerobic conditions when supplied with low amounts H2O2opens the possibility of using LPMOs as enzyme aids in biogas reactors to increase methane yields from lignocellulosic materials. We have explored this possibility by studying anaerobic digestion of various lignocellulosic materials: Avicel, milled spruce and birch wood, and a lignin-rich hydrolysis residue from steam-exploded birch. The digestions were added LPMOs and various cellulolytic enzyme cocktails and were carried out with or without addition of H2O2.ResultsIn several cases, enzyme addition had a beneficial effect on methane production, which was partly due to components present in the enzyme preparations. It was possible to detect LPMO activity during the initial phases of the anaerobic digestions of Avicel, and in some cases LPMO activity could be correlated with improved methane production from lignocellulosic materials. However, a positive effect on methane production was only seen when LPMOs were added together with cellulases, and never upon addition of LPMOs only. Generally, the experimental outcomes showed substrate-dependent variations in process efficiency and the importance of LPMOs and added H2O2. These differences could relate to variations in the type and content of lignin, which again will affect the activity of the LPMO, the fate of the added H2O2and the generation of potentially damaging reactive-oxygen species. The observed effects showed that the interplay between cellulases and LPMOs is important for the overall efficiency of the process.ConclusionThis study shows that it may be possible to harness the power of LPMOs in anaerobic digestion processes and improve biogas production, but also highlight the complexity of the reaction systems at hand. One complicating factor was that the enzymes themselves and other organic components in the enzyme preparations acted as substrates for biogas production, meaning that good control reactions were essential to detect effects caused by enzyme activity. As also observed during regular aerobic enzymatic digestion of lignocellulosic biomass, the type and contents of lignin in the substrates likely plays a major role in determining the impact of LPMOs and of cellulolytic enzymes in general. More work is needed to unravel the interplay between LPMOs, O2, H2O2, and the multitude of redox-active components found in anaerobic bioreactors degrading lignocellulosic substrates.