bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chitotriosidase: a biomarker of activity and severity in patients with sarcoidosis
Authors: Bennett David , Cameli Paolo , Lanzarone Nicola , Carobene Loredana , Bianchi Nicola , Fui Annalisa , Rizzi Luigi , Bergantini Laura , Cillis Giuseppe , d’Alessandro Miriana , Mazzei Maria Antonietta , Refini Rosa Metella , Sestini Piersante , Bargagli Elena , Rottoli Paola 
Published: January 2020

Abstract
Background
Serum chitotriosidase is a promising biomarker that has shown high specificity and sensitivity in patients with sarcoidosis. The aim of this study was to investigate correlations between serum chitotriosidase, clinical phenotypes, disease localizations and different radiological lung involvement and to identify clinical features associated with over-expression of chitotriosidase in a large cohort of sarcoidosis patients.

Methods
Chitotriosidase activity was evaluated in a population of 694 consecutive patients (males 39%, age 55.8 ± 12.8 years). Clinical and respiratory functional characteristics, Clinical Outcome Scale (COS) classification, clinical phenotypes proposed by the GenPhenResA project, and radiological assessment, including CT scan, were collected. Serum sampling and clinical and functional assessments at follow-up were also included.

Results
Significantly higher chitotriosidase activity was observed in sarcoidosis patients than in healthy controls (p < 0.0001). Evidence of lung fibrosis with reticular abnormalities and traction bronchiectasis at High resolution CT, presence of multiple extrapulmonary sarcoid localizations and increased 24-h urinary excretion of calcium were associated with significantly higher chitotriosidase activity (p < 0.005). Patients with remitted or minimal disease had lower values of chitotriosidase than patients with persistent disease. At follow-up, patients who required an increase in steroid dose showed an increase in its activity.

Conclusions
Chitotriosidase is a reliable biomarker of sarcoidosis. It is increased in patients with sarcoidosis correlating with disease activity, severity and multiorgan dissemination. Steroid therapy tended to reduce chitotriosidase expression, however it responded in cases of disease relapse.
Ongoing challenges in pulmonary fibrosis and insights from the nintedanib clinical programme
Authors: Valenzuela Claudia , Torrisi Sebastiano Emanuele , Kahn Nicolas , Quaresma Manuel , Stowasser Susanne , Kreuter Michael 
Published: January 2020

AbstractThe approvals of nintedanib and pirfenidone changed the treatment paradigm in idiopathic pulmonary fibrosis (IPF), and increased our understanding of the underlying disease mechanisms. Nonetheless, many challenges and unmet needs remain in the management of patients with IPF and other progressive fibrosing interstitial lung diseases.This review describes how the nintedanib clinical programme has helped to address some of these challenges. Data from this programme have informed changes to the IPF diagnostic guidelines, the timing of treatment initiation, and the assessment of disease progression. The use of nintedanib to treat patients with advanced lung function impairment, concomitant emphysema, patients awaiting lung transplantation and patients with IPF and lung cancer is discussed. The long-term use of nintedanib and an up-to-date summary of nintedanib in clinical practice are discussed. Directions for future research, namely emerging therapeutic options, precision medicine and other progressive fibrosing interstitial lung diseases, are described.Further developments in these areas should continue to improve patient outcomes.
Proteome analysis guided genetic engineering of Corynebacterium glutamicum S9114 for tween 40-triggered improvement in l-ornithine production
Authors: Jiang Yan , Huang Ming-Zhu , Chen Xue-Lan , Zhang Bin 
Published: January 2020

Abstract
Background
l-ornithine is a valuable amino acid with a wide range of applications in the pharmaceutical and food industries. However, the production of l-ornithine by fermentation cannot compete with other methods, because of the low titers produced with this technique. Development of fermentation techniques that result in a high yield of l-ornithine and efficient strategies for improving l-ornithine production are essential.

Results
This study demonstrates that tween 40, a surfactant promoter of the production of glutamate and arginine, improves l-ornithine production titers in engineered C. glutamicum S9114. The intracellular metabolism under tween 40 triggered fermentation conditions was explored using a quantitative proteomic approach, identifying 48 up-regulated and 132 down-regulated proteins when compared with the control. Numerous proteins were identified as membrane proteins or functional proteins involved in the biosynthesis of the cell wall. Modulation of those genes revealed that the overexpression of CgS9114_09558 and the deletion of CgS9114_13845, CgS9114_02593, and CgS9114_02058 improved the production of l-ornithine in the engineered strain of C. glutamicum Orn8. The final strain with all the exploratory metabolic engineering manipulations produced 25.46 g/L of l-ornithine, and a yield of 0.303 g l-ornithine per g glucose, which was 30.6% higher than that produced by the original strain (19.5 g/L).

Conclusion
These results clearly demonstrate the positive effect of tween 40 addition on l-ornithine accumulation. Proteome analysis was performed to examine the impact of tween 40 addition on the physiological changes in C. glutamicum Orn8 and the results showed several promising modulation targets for developing l-ornithine-producing strains.
Inequity in inpatient services utilization: a longitudinal comparative analysis of middle-aged and elderly patients with the chronic non-communicable diseases in China
Authors: Fu Xian-zhi , Wang Lian-ke , Sun Chang-qing , Wang Dong-dong , He Jun-jian , Tang Qi-xin , Zhou Qian-yu 
Published: January 2020

Abstract
Background
Aging and the chronic non-communicable diseases (NCDs) challenge the Chinese government in the process of providing hospitalization services fairly and reasonably. The Chinese government has developed the basic medical insurance system to solve the problem of “expensive medical cost and difficult medical services” for vulnerable groups and alleviate the unfair phenomenon. However, few studies have confirmed its effect through longitudinal comparison. This study aimed to explore the trend in the inequity of inpatient use among middle-aged and elderly individuals with NCDs in China.

Methods
This longitudinal comparative study was based on CHARLS data in 2011, 2013 and 2015. Concentration index (CI) was used to measure the variation trend of inequity of inpatient services utilization, while the decomposition method of the CI was applied to measure the factors contributing to inequity in inpatient services utilization. The effect of each factor on the change of inequity in inpatient services utilization was divided into the change of the elasticity and the change of inequality using the Oaxaca-type decomposition method.

Results
The affluent middle-aged and elderly patients with NCDs used more inpatient services than poor groups. The per capita household consumption expenditure (PCE) and Urban Employee Basic Medical Insurance (UEBMI) contributed to the decline in pro-rich inequality of inpatient use, while the New Rural Cooperative Medical Scheme (NRCMS) contributed to the decline in pro-poor inequality of inpatient use.

Conclusions
There was a certain degree of pro-rich unfairness in the probability and frequency of inpatient services utilization for middle-aged and elderly individuals with NCDs in China. The decrease of pro-wealth contribution of PCE and UEBMI offset the decrease of pro-poor contribution of NRCMS, and improved the equity of inpatient services utilization, favoring poor people.
Beliefs about cannabis at the time of legalization in Canada: results from a general population survey
Authors: Cunningham John A. 
Published: January 2020

Abstract
Aims
Cannabis became a legally available drug in Canada in October of 2018. The objective of this study was to examine beliefs about cannabis use at the time of legalization among past year cannabis users, those who had used cannabis but not in the last year, and people who had never used cannabis.

Design and methods
A survey of 813 participants, 18 years and over, and identified using random digit dialing methods, was made of the Canadian general population. Among other items, participants were asked a series of questions about their beliefs regarding cannabis use and recovery.

Results
Compared to never and ever users, participants who used cannabis in the last year regarded cannabis as less of a societal problem (mean [SD] past year use = 3.8 [2.4] versus 6.4 [2.6] and 6.0 [2.4] respectively, p = .001), than people were less likely to become addicted to cannabis if they tried it (past year use = 13.3% versus 48.3% and 25.1%, p = .001), and a larger proportion believed that recovery from cannabis without treatment was likely (past year use = 40.8% versus 14.2% and 19.3%, p = .001). All groups were equally positive of the chances of recovering from cannabis addiction with treatment (p = .72).

Discussion and conclusion
Beliefs about cannabis use vary substantially between those who have used the drug in the past year and those who have not. Replication of the survey at a later date is merited in order to assess the ways in which beliefs about cannabis evolve after an extended period of cannabis being available as a legal drug.
Quality of life in children with infrequent congenital heart defects: cohort study with one-year of follow-up
Authors: Moreno-Medina Karen , Barrera-Castañeda Magally , Vargas-Acevedo Catalina , García-Torres Alberto E. , Ronderos Miguel , Huertas-Quiñones Manuel , Cabrera Silvana , Domínguez María Teresa , Sandoval Reyes Nestor , Dennis Rodolfo J. 
Published: January 2020

Abstract
Background
The evidence regarding patient related outcomes in children with infrequent congenital heart defects (I-CHD) is very limited. We sought to measure quality of life (QoL) in children with I-CHD, and secondarily, to describe QoL changes after one-year of follow-up, self-reported by children and through their caregivers’ perspective.

Methods
We assembled a cohort of children diagnosed with an I-CHD in a cardiovascular referral center in Colombia, between August 2016 and September 2018. At baseline and at one-year follow-up, a clinical psychology assessment was performed to establish perception of QoL. The Pediatric Quality of Life Inventory (PedsQL) 4.0 scale was used in both general and cardiac modules for patients and for their caregivers. We used a Mann-Whitney U test to compare scores for general and cardiac modules between patients and caregivers, while a Wilcoxon test was used to compared patients’ and caregivers’ baseline and follow-up scores. Results are presented as median and interquartile range.

Results
To date, QoL evaluation at one-year follow-up has been achieved in 112/157 patients (71%). Self-reported scores in general and cardiac modules were higher than the QoL perceived through their caregivers, both at baseline and after one-year of follow-up. When compared, there was no statistically significant difference in general module scores at baseline between patients (median = 74.4, IQR = 64.1–80.4) and caregivers scores (median = 68.4, IQR = 59.6–83.7), p = 0.296. On the contrary, there was a statistical difference in baseline scores in the cardiac module between patients (median = 79.6, IQR = 69.7–87.4) and caregivers (median = 73.6, IQR = 62.6–84.3), p = 0.019. At one-year of follow-up, scores for the general module between patients (median = 72.8, IQR = 59.2–85.9) and caregivers (median = 69.9, IQR = 58.1–83.7) were not statistically different (p = 0.332). Finally, a significant difference was found for cardiac module scores between patient (median = 75.0, IQR = 67.1–87.1) and caregivers (median = 73.1, IQR = 59.5–83.8), p = 0.034.

Conclusions
QoL in children with I-CHD can be compromised. However, children have a better perception of their QoL when compared with their caregivers’ assessments. To provide high-quality care, besides a thorough clinical evaluation, QoL directly elicited by the child should be an essential aspect in the integral management of I-CHD.
Classical complement cascade initiating C1q protein within neurons in the aged rhesus macaque dorsolateral prefrontal cortex
Authors: Datta Dibyadeep , Leslie Shannon N. , Morozov Yury M. , Duque Alvaro , Rakic Pasko , van Dyck Christopher H. , Nairn Angus C. , Arnsten Amy F. T. 
Published: January 2020

Abstract
Background
Cognitive impairment in schizophrenia, aging, and Alzheimer’s disease is associated with spine and synapse loss from the dorsolateral prefrontal cortex (dlPFC) layer III. Complement cascade signaling is critical in driving spine loss and disease pathogenesis. Complement signaling is initiated by C1q, which tags synapses for elimination. C1q is thought to be expressed predominately by microglia, but its expression in primate dlPFC has never been examined. The current study assayed C1q levels in aging primate dlPFC and rat medial PFC (mPFC) and used immunoelectron microscopy (immunoEM), immunoblotting, and co-immunoprecipitation (co-IP) to reveal the precise anatomical distribution and interactions of C1q.

Methods
Age-related changes in C1q levels in rhesus macaque dlPFC and rat mPFC were examined using immunoblotting. High-spatial resolution immunoEM was used to interrogate the subcellular localization of C1q in aged macaque layer III dlPFC and aged rat layer III mPFC. co-IP techniques quantified protein-protein interactions for C1q and proteins associated with excitatory and inhibitory synapses in macaque dlPFC.

Results
C1q levels were markedly increased in the aged macaque dlPFC. Ultrastructural localization found the expected C1q localization in glia, including those ensheathing synapses, but also revealed extensive localization within neurons. C1q was found near synapses, within terminals and in spines, but was also observed in dendrites, often near abnormal mitochondria. Similar analyses in aging rat mPFC corroborated the findings in rhesus macaques. C1q protein increasingly associated with PSD95 with age in macaque, consistent with its synaptic localization as evidenced by EM.

Conclusions
These findings reveal novel, intra-neuronal distribution patterns for C1q in the aging primate cortex, including evidence of C1q in dendrites. They suggest that age-related changes in the dlPFC may increase C1q expression and synaptic tagging for glial phagocytosis, a possible mechanism for age-related degeneration.
High levels of dietary methionine improves sitagliptin-induced hepatotoxicity by attenuating oxidative stress in hypercholesterolemic rats
Authors: Kumar Avinash , Pathak Rashmi , Palfrey Henry A. , Stone Kirsten P. , Gettys Thomas W. , Murthy Subramanyam N. 
Published: January 2020

Abstract
Background
Both cholesterol (Cho) and methionine (Met, a precursor for homocysteine) are risk factors for fatty liver disease. Since Western diets are rich in Cho and Met, we investigated the hepatic effects of feeding a diet enriched in Met and Cho. Further, based on the reported anti-oxidative and lipid lowering properties of sitagliptin (an antidiabetic drug), we tested whether it could counteract the negative effects of high Cho and Met. We therefore hypothesized that sitagliptin would ameliorate the development of liver pathology that is produced by feeding diets rich in either Cho, Met, or both.

Methods
Male Sprague Dawley rats were fed ad libitum a) control diet, or b) high Met or c) high Cho, or d) high Met + high Cho diets for 35 days. From day 10 to 35, 50% of rats in each dietary group were gavaged with either vehicle or an aqueous suspension of sitagliptin (100 mg/kg/day). Liver samples were harvested for histological, molecular, and biochemical analyses.

Results
The high Cho diet produced significant hepatic steatosis which was unaffected by sitagliptin. Contrary to expectation, sitagliptin exacerbated expression of hepatic markers of oxidative stress and fibrosis in rats fed high Cho. Corresponding increases in 4-hydroxynonenal adducts and collagen deposition were demonstrated by immunohistochemistry and sirius red staining. These hepatic changes were absent in rats on the high Met diet and they were comparable to controls. The inclusion of Met in the high Cho diet resulted in significant reduction of the hepatic steatosis, oxidative stress, and fibrosis produced by high Cho alone.

Conclusion
Sitagliptin exacerbated the effects of high Cho on both oxidative stress and fibrosis, resulting in NASH like symptoms that were significantly reversed by the inclusion of Met.
Effectiveness of a new approach for exclusive breastfeeding counselling on breastfeeding prevalence, infant growth velocity and postpartum weight loss in overweight or obese women: protocol for a randomized controlled trial
Authors: Aldana-Parra Fanny , Olaya Gilma , Fewtrell Mary 
Published: January 2020

Abstract
Background
Maternal overweight, infant feeding and early growth velocity are risk factors for obesity later in life. The first one thousand days are a window of opportunity to program health and disease. Exclusive breastfeeding may protect against obesity; however, it is not consistently practiced. Obesity rates have been increasing worldwide. Overweight or obese women have lower rates of breastfeeding and face mechanical, psychological and biological difficulties. Breastfeeding counselling is a successful strategy to support breastfeeding in normal weight women; but there is a lack of evidence on its effectiveness in overweight women. Our purpose is to evaluate a new approach to exclusive breastfeeding counselling based on Carl Rogers’ Centred-Client Theory in overweight women, and to examine effects on breastfeeding prevalence, infant growth velocity and maternal postpartum weight loss.

Methods
A two-arm simple randomized controlled trial will be conducted in overweight and obese women recruited in a Baby Friendly Hospital in Bogotá, Colombia. The intervention is exclusive breastfeeding counselling based on Rogers’ theory but adapted for overweight women; it will be performed during the last month of pregnancy, 24 h after delivery and during early infancy (1 and 3 months postpartum). The primary outcomes will be exclusive breastfeeding prevalence, infant growth velocity and maternal weight loss from birth up to 4 months after delivery; and the secondary outcomes will be prolactin and macronutrient levels in breast milk and serum prolactin levels. Intention to treat analysis will be performed to estimate the effect of the new counselling approach compared to standard management on the prevalence of exclusive breastfeeding, infant growth velocity and maternal weight loss.

Discussion
We hypothesize that the intervention will result in an increase in the initiation and maintenance of exclusive breastfeeding, allowing adequate infant growth velocity and maternal weight loss after delivery. It is hoped that the results of this trial will provide evidence to support public health policy on supporting breastfeeding in this vulnerable group of women.

Trial registration
(UTN) U1111–1228-9913 February 20th 2019; ISRCTN15922904
February 27th 2019, retrospectively registered.
Definitive chemoradiotherapy in patients with squamous cell cancers of the head and neck - results from an unselected cohort of the clinical cooperation group “Personalized Radiotherapy in Head and Neck Cancer”
Authors: Schüttrumpf Lars , Marschner Sebastian , Scheu Katrin , Hess Julia , Rietzler Sibylle , Walch Axel , Baumeister Philipp , Kirchner Thomas , Ganswindt Ute , Zitzelsberger Horst , Belka Claus , Maihoefer Cornelius 
Published: January 2020

Abstract
Background
Definitive chemoradiotherapy (dCRT) is a standard treatment for patients with locally advanced head and neck cancer. There is a clinical need for a stratification of this prognostically heterogeneous group of tumors in order to optimize treatment of individual patients. We retrospectively reviewed all patients with head and neck squamous cell carcinoma (HNSCC) of the oral cavity, oropharynx, hypopharynx, or larynx, treated with dCRT from 09/2008 until 03/2016 at the Department of Radiation Oncology, LMU Munich. Here we report the clinical results of the cohort which represent the basis for biomarker discovery and molecular genetic research within the framework of a clinical cooperation group.

Methods
Patient data were collected and analyzed for outcome and treatment failures with regard to previously described and established risk factors.

Results
We identified 184 patients with a median follow-up of 65 months and a median age of 64 years. Patients received dCRT with a median dose of 70 Gy and simultaneous chemotherapy in 90.2% of cases, mostly mitomycin C / 5-FU in concordance with the ARO 95–06 trial. The actuarial 3-year overall survival (OS), local, locoregional and distant failure rates were 42.7, 29.8, 34.0 and 23.4%, respectively. Human papillomavirus-associated oropharynx cancer (HPVOPC) and smaller gross tumor volume were associated with significantly improved locoregional tumor control rate, disease-free survival (DFS) and OS in multivariate analysis. Additionally, lower hemoglobin levels were significantly associated with impaired DFS und OS in univariate analysis. The extent of lymph node involvement was associated with distant failure, DFS and OS. Moreover, 92 patients (50%) of our cohort have been treated in concordance with the ARO 95–06 study, corroborating the results of this study.

Conclusion
Our cohort is a large unselected monocentric cohort of HNSCC patients treated with dCRT. Tumor control rates and survival rates compare favorably with the results of previously published reports. The clinical data, together with the available tumor samples from biopsies, will allow translational research based on molecular genetic analyses.
HPV-related oropharyngeal cancer prevalence in a middle eastern population using E6/E7 PCR
Authors: Maroun Christopher A. , Al Feghali Karine , Traboulsi Henri , Dabbous Helene , Abbas Fatmeh , Dunya Gabriel , Ziade Georges , Mahfouz Rami , Youssef Bassem , Tamim Hani , Geara Fady , Khalifeh Ibrahim , Moukarbel Roger V. 
Published: January 2020

AbstractBackgroundGiven the paucity of data and widely variable rates that have been reported, the main objective of this study was to examine the prevalence of HPV-positivity in oropharyngeal squamous cell carcinoma (OPSCC) in Middle Eastern patients presenting to one of the region’s largest tertiary care centers using polymerase chain reaction (PCR) amplification of the HPV E6/E7 oncogenes, a highly sensitive and specific method of detection.MethodsMedical charts and archived pathological specimens were obtained for patients diagnosed with biopsy proven oropharyngeal cancer who presented to the American University of Beirut Medical Center between 1972 and 2017. DNA was extracted from paraffin-embedded specimens and tested for 30 high-risk and low-risk papilloma viruses using the PCR-based EUROarray HPV kit (EuroImmun).ResultsA total of 57 patients with oropharyngeal cancer were initially identified; only 34 met inclusion/exclusion criteria and were included in the present study. Most patients were males (73.5%) from Lebanon (79.4%). The most common primary tumor site was in the base of tongue (50%), followed by the tonsil (41.2%). The majority of patients (85.3%) tested positive for HPV DNA.ConclusionThe prevalence of HPV-positivity amongst Middle Eastern OPSCC patients, specifically those from Lebanon, may be far greater than previously thought. The Lebanese population and other neighboring Middle Eastern countries may require a more vigilant approach towards HPV detection and awareness. On an international level, further research is required to better elucidate non-classical mechanisms of HPV exposure and transmission.