bluuebunny/crossref_metadata_2025_split huggingface dataset:
Review article: iron disturbances in chronic liver diseases other than haemochromatosis – pathogenic, prognostic, and therapeutic implications
Authors: Czaja Albert J. 
Published: February 2019

SummaryBackgroundDisturbances in iron regulation have been described in diverse chronic liver diseases other than hereditary haemochromatosis, and iron toxicity may worsen liver injury and outcome.AimsTo describe manifestations and consequences of iron dysregulation in chronic liver diseases apart from hereditary haemochromatosis and to encourage investigations that clarify pathogenic mechanisms, define risk thresholds for iron toxicity, and direct managementMethodsEnglish abstracts were identified in PubMed by multiple search terms. Full length articles were selected for review, and secondary and tertiary bibliographies were developed.ResultsHyperferritinemia is present in 4%‐65% of patients with non‐alcoholic fatty liver disease, autoimmune hepatitis, chronic viral hepatitis, or alcoholic liver disease, and hepatic iron content is increased in 11%‐52%. Heterozygosity for the C282Y mutation is present in 17%‐48%, but this has not uniformly distinguished patients with adverse outcomes. An inappropriately low serum hepcidin level has characterised most chronic liver diseases with the exception of non‐alcoholic fatty liver disease, and the finding has been associated mainly with suppression of transcriptional activity of the hepcidin gene. Iron overload has been associated with oxidative stress, advanced fibrosis and decreased survival, and promising therapies beyond phlebotomy and oral iron chelation have included hepcidin agonists.ConclusionsIron dysregulation is common in chronic liver diseases other than hereditary haemochromatosis, and has been associated with liver toxicity and poor prognosis. Further evaluation of iron overload as a co‐morbid factor should identify the key pathogenic disturbances, establish the risk threshold for iron toxicity, and promote molecular interventions.
Corporate Political Activity and Free Riding under Market Uncertainty: An Investigation of TARP Funding
Authors: Brown Lee Warren , De Leon John A. , Rasheed Abdul A. 
Published: February 2019

AbstractGiven that the benefits of Corporate Political Activity (CPA) are usually granted in the form of favorable industry regulation that benefits all industry participants rather than a single firm, small politically inactive firms are often able to take advantage of the benefits from CPA without investing in them. We argue that the free‐riding problem is context specific. Situations of extreme uncertainty create institutional voids that enable individual firms to more fully appropriate the returns from their CPA. In this paper, we examine the influence that CPA had on the U.S. government’s disbursements of TARP funding in 2008. We find that politically active firms were able to avoid the free‐rider problem by obtaining more instances of TARP funding when compared to firms that were not politically active. In addition to being more likely to receive TARP funds, politically active firms received larger amounts of TARP funding than those firms who were not politically active.
A semiphysiological population pharmacokinetic model of agomelatine and its metabolites in Chinese healthy volunteers
Authors: Xie Feifan , Vermeulen An , Colin Pieter , Cheng Zeneng 
Published: February 2019

AimsAgomelatine is an antidepressant for major depressive disorders. It undergoes extensive first‐pass hepatic metabolism and displays irregular absorption profiles and large interindividual variability (IIV) and interoccasion variability of pharmacokinetics. The objective of this study was to characterize the complex pharmacokinetics of agomelatine and its metabolites in healthy subjects.MethodsPlasma concentration–time data of agomelatine and its metabolites were collected from a 4‐period, cross‐over bioequivalence study, in which 44 healthy subjects received 25 mg agomelatine tablets orally. Nonlinear mixed effects modelling was used to characterize the pharmacokinetics and variability of agomelatine and its metabolites. Deterministic simulations were carried out to investigate the influence of pathological changes due to liver disease on agomelatine pharmacokinetics.ResultsA semiphysiological pharmacokinetic model with parallel first‐order absorption and a well‐stirred liver compartment adequately described the data. The estimated IIV and interoccasion variability of the intrinsic clearance of agomelatine were 130.8% and 28.5%, respectively. The IIV of the intrinsic clearance turned out to be the main cause of the variability of area under the curve‐based agomelatine exposure. Simulations demonstrated that a reduction in intrinsic clearance or liver blood flow, and an increase in free drug fraction had a rather modest influence on agomelatine exposures (range: −50 to 200%). Portosystemic shunting, however, substantially elevated agomelatine exposure by 12.6–109.1‐fold.ConclusionsA semiphysiological pharmacokinetic model incorporating first‐pass hepatic extraction was developed for agomelatine and its main metabolites. The portosystemic shunting associated with liver disease might lead to significant alterations of agomelatine pharmacokinetics, and lead to substantially increased exposure.
The heterogeneous nature of water well fluoride levels in Sri Lanka: An opportunity to mitigate the dental fluorosis
Authors: Ranasinghe Nirosha , Kruger Estie , Chandrajith Rohana , Tennant Marc 
Published: February 2019

AbstractObjectivesThe study aimed to use Geographic Information Systems (GIS) to investigate the spatial distribution of the concentration of fluoride (F) in groundwater resources of Sri Lanka, and the geographic accessibility to an alternative water source having a low or safe F limit to mitigate dental fluorosis.MethodsThe study used randomly collected (6107) groundwater samples from Sri Lanka and categorized them as “dentally optimal” and “unsafe” based on their F content. The minimum distance from an identified high F source (above dentally optimal level) to a safe groundwater source was determined using geospatial analysis.ResultsDentally optimal F sources (<1 and <1.5 mg/L) were identified among the high F groundwater sources (>2 mg/L), some even within a walking distance of 500 m. Results indicated that 26% of dentally unsafe groundwater sources (2.0 mg/L+ wells) had a low F source (<1.0 mg/L) available within a distance of 500 m. It was also evident that 39% of high F wells (2.0 mg/L+ wells) had a low F well (<1.5 mg/L) within a distance of 500 m, if the WHO guideline value for optimal F levels (1.5 mg/L) was assigned as the safe F limit.ConclusionThe spatial approach demonstrated a reasonable access to alternative water sources with low or safe F limit in endemic fluorosis areas. Optimizing the use of accessible low F sources is highly recommended as the first‐line option to mitigate dental fluorosis in Sri Lanka since the defluoridation methods introduced in past did not provide sustainable oral health solutions for the inhabitants in high‐risk areas.
Depressive symptoms in inflammatory bowel disease: an extraintestinal manifestation of inflammation?
Authors: Moulton C D , Pavlidis P , Norton C , Norton S , Pariante C , Hayee B , Powell N 
Published: February 2019

Summary
Depressive symptoms are reported by more than 20% of people with inflammatory bowel disease (IBD), while sleep difficulties and fatigue are even more common. Co-morbid depressive symptoms predict a poor IBD course, including increased risk of relapse and surgery, which is inconsistently improved by psychological treatments. Rather than being distinct systems, there is compelling evidence for bidirectional communication between gut and brain, driven by neural, metabolic, endocrine and inflammatory mediators. An emerging concept is that depressive symptoms may be mechanistically linked to excess inflammation and dysregulation of the gut–brain axis. Given the close link between the intestinal microbiota and host immune responses, patients prone to shifts in their intestinal microbiome, including smokers, those with poor diet and early life stress, may be exposed to exaggerated immune responses. Excess inflammation is associated with brain changes (depressive symptoms, fatigue, sleep difficulties) and worsening gastrointestinal symptoms, which are exacerbated by psychological distress. Equally, treatments both for depressive symptoms and IBD provide opportunities to break this cycle by reducing the causes and effects of inflammation. As well as addressing potential risk factors such as smoking and diet, treatments to alter the microbiome may reduce depressive symptoms. Observational evidence suggests that anti-inflammatory treatments for IBD may improve co-morbid depressive symptoms correlating with reduction in inflammation. With a growing range of treatments targeting inflammation centrally, peripherally and in the gut, IBD provides a unique model to understand the interplay between brain and gut in the pathogenesis of depressive symptoms, both in IBD and in the whole population.
Automatic Generation of Vivid LEGO Architectural Sculptures
Authors: Zhou J. , Chen X. , Xu Y. 
Published: February 2019

AbstractBrick elements are very popular and have been widely used in many areas, such as toy design and architectural fields. Designing a vivid brick sculpture to represent a three‐dimensional (3D) model is a very challenging task, which requires professional skills and experience to convey unique visual characteristics. We introduce an automatic system to convert an architectural model into a LEGO sculpture while preserving the original model's shape features. Unlike previous legolization techniques that generate a LEGO sculpture exactly based on the input model's voxel representation, we extract the model's visual features, including repeating components, shape details and planarity. Then, we translate these visual features into the final LEGO sculpture by employing various brick types. We propose a deformation algorithm in order to resolve discrepancies between an input mesh's continuous 3D shape and the discrete positions of bricks in a LEGO sculpture. We evaluate our system on various architectural models and compare our method with previous voxelization‐based methods. The results demonstrate that our approach successfully conveys important visual features from digital models and generates vivid LEGO sculptures.
Feasibility and acceptability of adherence support for direct acting antiviral therapy for hepatitis C in a low‐threshold primary health‐care opioid agonist treatment program
Authors: Chronister Karen J. , Lothian Rebecca , Gilliver Rosie , Kearley John , Read Phillip 
Published: February 2019

AbstractIntroduction and AimsTo maximise the benefits of direct acting antivirals in Australia, innovative options for marginalised populations to receive daily or weekly medication may be beneficial. This study evaluated the feasibility and acceptability of direct acting antivirals provision by leveraging an opioid agonist treatment program to support adherence regardless of opioid agonist treatment enrolment.Design and MethodsFeasibility was evaluated by monitoring selection of dosing options by clients initiating direct acting antivirals during the first 6 months. Client acceptability was assessed using a cross‐sectional survey after 6 months. Pre‐ and post‐implementation surveys of attitudes and concerns regarding the program were compared to evaluate staff acceptability.ResultsAmong 79 clients commencing direct acting antivirals, 30 (38%) chose adherence support. Among these, 12 (40%) were not simultaneously enrolled in opioid agonist treatment. Clients were satisfied with service provision and access despite introducing daily dosing. All highly marginalised clients receiving direct acting antivirals with adherence support found this helpful. Staff concerns identified prior to the program proved unfounded.Discussion and ConclusionsThis study demonstrates providing adherence support for direct acting antivirals regardless of client participation in opioid agonist treatment is both feasible and acceptable with minimal impact on service provision. Availability of direct acting antivirals in opioid agonist treatment or primary health‐care settings expands the pool of people who may receive effective treatment for hepatitis C virus and reduces treatment barriers.
S2k Guidelines for Cutaneous Basal Cell Carcinoma – Part 2: Treatment, Prevention and Follow‐up
Authors: Lang Berenice M. , Balermpas Panagiotis , Bauer Andrea , Blum Andreas , Brölsch G. Felix , Dirschka Thomas , Follmann Markus , Frank Jorge , Frerich Bernhard , Fritz Klaus , Hauschild Axel , Heindl Ludwig M. , Howaldt Hans‐Peter , Ihrler Stephan , Kakkassery Vinodh , Klumpp Bernhard , Krause‐Bergmann Albrecht , Löser Christoph , Meissner Markus , Sachse Michael M. , Schlaak Max , Schön Michael P. , Tischendorf Lutz , Tronnier Michael , Vordermark Dirk , Welzel Julia , Weichenthal Michael , Wiegand Susanne , Kaufmann Roland , Grabbe Stephan 
Published: February 2019

SummaryBasal cell carcinoma (BCC) is the most common malignant tumor among fair‐skinned individuals, and its incidence had been steadily rising in the past decades. In order to maintain the highest quality of patient care possible, the German S2k guidelines were updated following a systematic literature search and with the participation of all professional societies and associations involved in the management of the disease. Part 2 addresses issues such as proper risk stratification, the various therapeutic approaches, and prevention as well as follow‐up of patients with basal cell carcinoma.
Hautentzündungen mit Arthritis, Synovitis und Enthesitis. Teil 2: Rheumatoide Arthritis, reaktive Arthritis, Morbus Reiter, Lyme‐Borreliose, Dermatomyositis und Lupus erythematodes
Authors: Schempp Christoph M. , Schauer Franziska , Huhn Christian K. , Venhoff Nils , Finzel Stephanie 
Published: February 2019

ZusammenfassungDie Syndrome mit gleichzeitiger Entzündung von Haut und Gelenken stellen oft eine Herausforderung für Dermatologen und Rheumatologen dar. Im vorausgehenden ersten Teil dieser Übersicht wurden die Psoriasisarthritis und die autoinflammatorischen Erkrankungen SAPHO‐Syndrom, Morbus Still und Morbus Behçet behandelt. Hier folgen rheumatoide Arthritis, reaktive Arthritis, Morbus Reiter und Lyme‐Borreliose. Anschließend werden die Dermatomyositis und der Lupus erythematodes besprochen, häufige autoimmunologische Krankheiten, bei denen neben Haut oft auch die Gelenke betroffen sind. Jedes Krankheitsbild wird hinsichtlich Epidemiologie, Pathogenese, Klinik, Diagnostik und Therapie abgehandelt.
Diabetes distress in young adults with early‐onset Type 1 diabetes and its prospective relationship with HbA1cand health status
Authors: Stahl‐Pehe A. , Glaubitz L. , Bächle C. , Lange K. , Castillo K. , Tönnies T. , Yossa R. , Holl R. W. , Rosenbauer J. 
Published: February 2019

AbstractAimThis study aimed to determine cross‐sectional relationships between diabetes distress and health‐related variables, and prospective associations between diabetes distress and future glycaemic control (HbA1c) and health status among young adults with early‐onset Type 1 diabetes.MethodsData were collected from a nationwide cohort study of adults whose Type 1 diabetes onset occurred from 0 to 4 years of age during 1993–2002. Questionnaire surveys were conducted in 2012–2013 and 2015–2016 (N = 584). Diabetes distress was assessed via the Problem Areas in Diabetes (PAID) scale (0–100 points), depressive symptoms via the Patient Health Questionnaire‐9 (PHQ‐9) and health status via the 12‐Item Short Form Health Survey (SF‐12) questionnaire. Multivariable linear regression analyses were applied to cross‐sectional and longitudinal data.ResultsIn the cross‐sectional analyses, higherPAIDscale total scores (representing higher distress levels) were observed in women than in men and in participants with more severe depressive symptoms.PAIDscores were lower in individuals with better physical and mental health. A 1 mmol/mol increase in HbA1cwas associated with a 0.28‐point increase [95% confidence interval (95%CI) 0.20, 0.36] in diabetes distress. In longitudinal analyses adjusting for age, sex, socio‐economic index and HbA1cat baseline, a 10‐point higherPAIDscore at baseline was associated with a 1.82 mmol/mol higher HbA1clevel (95%CI0.43, 3.20) and a 2.48‐point lowerSF‐12 mental health score (95%CI−3.55, −1.42) three years later.ConclusionsThe cross‐sectional and longitudinal analyses results suggest that diabetes distress impairs health‐related outcomes in young adults with early‐onset diabetes.
Pharmaco‐electroencephalographic responses in the rat differ between active and inactive locomotor states
Authors: Hansen Ingeborg H. , Agerskov Claus , Arvastson Lars , Bastlund Jesper F. , Sørensen Helge B. D. , Herrik Kjartan F. 
Published: February 2019

AbstractQuantitative electroencephalography from freely moving rats is commonly used as a translational tool for predicting drug‐effects in humans. We hypothesized that drug‐effects may be expressed differently depending on whether the rat is in active locomotion or sitting still during recording sessions, and proposed automatic state‐detection as a viable tool for estimating drug‐effects free of hypo‐/hyperlocomotion‐induced effects. We aimed at developing a fully automatic and validated method for detecting two behavioural states: active and inactive, in one‐second intervals and to use the method for evaluating ketamine, DOI, d‐cycloserine, d‐amphetamine, and diazepam effects specifically within each state. The developed state‐detector attained high precision with more than 90% of the detected time correctly classified, and multiple differences between the two detected states were discovered. Ketamine‐induced delta activity was found specifically related to locomotion. Ketamine and DOI suppressed theta and beta oscillations exclusively during inactivity. Characteristic gamma and high‐frequency oscillations (HFO) enhancements of the NMDAR and 5HT2A modulators, speculated associated with locomotion, were profound and often largest during the inactive state. State‐specific analyses, theoretically eliminating biases from altered occurrence of locomotion, revealed only few effects of d‐amphetamine and diazepam. Overall, drug‐effects were most abundant in the inactive state. In conclusion, this new validated and automatic locomotion state‐detection method enables fast and reliable state‐specific analysis facilitating discovery of state‐dependent drug‐effects and control for altered occurrence of locomotion. This may ultimately lead to better cross‐species translation of electrophysiological effects of pharmacological modulations.
Effect of oxidative stress in rostral ventrolateral medulla on sympathetic hyperactivity after traumatic brain injury
Authors: Chen Jigang , Chen Wen , Han Kaiwei , Qi Enbo , Chen Rongbin , Yu Minkun , Hou Lijun , Lv Liquan 
Published: February 2019

AbstractSympathetic hyperactivity occurs in a subgroup of patients after traumatic brain injury (TBI). The rostral ventrolateral medulla (RVLM) is a key region for the activity of sympathetic nervous system. Oxidative stress in the RVLM is proved to be responsible for the increased level of sympathetic activity in animal models of hypertension and heart failure. In this study, we investigated whether oxidative stress in the RVLM contributed to the development of sympathetic hyperactivity after TBI in rats. Model of diffuse axonal injury was induced using Sprague‐Dawley rats, and level of mean arterial pressure (MAP) and plasma Norepinephrine (NE) was measured to evaluate the sympathetic activity. For the assessment of oxidative stress, expression of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) in the RVLM was determined. Microinjection of Tempol into the RVLM was performed to determine the effect of oxidative stress on sympathetic hyperactivity. According to the results, TBI led to elevated MAP and plasma NE in rats. It also induced a significantly increased level of ROS, MDA production and decreased level of SOD in the RVLM. The sympathetic activity, ROS, and MDA in the RVLM decreased significantly after microinjection of Tempol. Therefore, the present results suggested that oxidative stress in the RVLM was involved in the development of sympathetic hyperactivity following TBI.
Emergency surgery and American Society of Anesthesiologists physical status score are the most influential risk factors of death in nonagenarian surgical patients
Authors: Fariña‐Castro Roberto , Roque‐Castellano Cristina , Artiles‐Armas Manuel , Marchena‐Gómez Joaquín 
Published: February 2019

AimThe number of nonagenarians undergoing surgery has increased considerably in recent decades as a result of population aging. Greater knowledge of the most influential factors affecting perioperative morbidity and mortality would improve the quality of care and provision of health resources for these patients. The objective of the present study was to analyze the perioperative mortality, and its most determinant factors, among nonagenarian patients who underwent a surgical procedure in the Department of General and Digestive Surgery.MethodsA retrospective descriptive study was carried out in a cohort of 159 consecutive non‐selected surgical nonagenarian patients. Clinical data, type of operation, perioperative hemodynamic instability, the need for blood transfusion and medical/surgical complications were evaluated as predictor variables. The outcome variable was operative mortality.ResultsThe mean age was 91.8 years (SD ± 2.0); there were 60 men (37.7%) and 99 (62.3%) women. Perioperative mortality was 28.93% (46 patients). The variables age (P = 0.025), American Society of Anesthesiologists physical status score (P < 0.001), neoplastic pathology (P = 0.025), intestinal surgery (P = 0.001), emergent surgery (P ≤ 0.001), perioperative blood transfusion (P = 0.003), postoperative medical complications (P < 0.001) and surgical complications (P = 0.022) showed a statistically significant correlation with mortality. American Society of Anesthesiologists physical status score (P = 0.007), emergent surgery (P < 0.032) and perioperative blood transfusion (P = 0.047) were identified as independent predictors of mortality.ConclusionsSurgery should not be denied to nonagenarian patients based only on their age. Emergency surgery and American Society of Anesthesiologists physical status classification are the most significant factors when deciding whether to intervene. Geriatr Gerontol Int 2019; 19: 293–298.
Spironolactone‐induced XPB degradation depends on CDK7 kinase and SCFFBXL18 E3 ligase
Authors: Ueda Masanobu , Matsuura Kenkyo , Kawai Hidehiko , Wakasugi Mitsuo , Matsunaga Tsukasa 
Published: February 2019

AbstractThe multisubunit complex transcription factor IIH (TFIIH) has dual functions in transcriptional initiation and nucleotide excision repair (NER). TFIIH is comprised of two subcomplexes, the core subcomplex (seven subunits) including XPB and XPD helicases and the cyclin‐dependent kinase (CDK)‐activating kinase (CAK) subcomplex (three subunits) containing CDK7 kinase. Recently, it has been reported that spironolactone, an anti‐aldosterone drug, inhibits cellular NER by inducing proteasomal degradation of XPB and potentiates the cytotoxicity of platinum‐based drugs in cancer cells, suggesting possible drug repositioning. In this study, we have tried to uncover the mechanism underlying the chemical‐induced XPB destabilization. Based on siRNA library screening and subsequent analyses, we identified SCFFBXL18 E3 ligase consisting of Skp1, Cul1, F‐box protein FBXL18 and Rbx1 responsible for spironolactone‐induced XPB polyubiquitination and degradation. In addition, we showed that CDK7 kinase activity is required for this process. Finally, we found that the Ser90 residue of XPB is essential for the chemical‐induced destabilization. These results led us to propose a model that spironolactone may trigger the phosphorylation of XPB at Ser90 by CDK7, which promotes the recognition and polyubiquitination of XPB by SCFFBXL18 for proteasomal degradation.