bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical outcomes of patients with active rheumatoid arthritis with normal acute phase reactant values
Authors: Chung Min Kyung , Park Bohyun , Kim In Je , Cho Soo‐Kyung , Kim Dam , Sung Yoon‐Kyoung , Choi Chan‐Bum , Choe Jung‐Yoon , Chung Won Tae , Hong Seung‐Jae , Kim Tae‐Hwan , Koh Eunmi , Lee Shin‐Seok , Yoon Bo Young , Park Hyesook , Bae Sang‐Cheol , Lee Jisoo 
Published: January 2019

AbstractAimDespite high clinical disease activity, some patients with active rheumatoid arthritis (RA) have normal acute phase reactant (APR) values. This study aimed to determine the clinical outcomes of active RA patients with normal APR values.MethodOf 5376 patients with RA enrolled in the Korean observational study network for arthritis (KORONA) registry, 400 patients with disease duration of <2 years who had Clinical Disease Activity Index (CDAI) score of >2.8 at baseline, biologic‐naïve, and erythrocyte sedimentation rate (ESR) and C‐reactive protein (CRP) drawn at both baseline and 2‐year follow‐up visits were identified. Patients were grouped according to baseline APR levels: normal APRs, one APR elevated, and both APRs elevated.ResultsBaseline tender and swollen joint counts, mean CDAI and Health Assessment Questionnaire‐Disability Index (HAQ‐DI) scores were significantly lower in the normal APRs group compared with APR‐elevated groups (P < 0.0001). At 2‐year follow‐up, mean CDAI scores, HAQ‐DI, and percentage of the patient achieving remission were not significantly different between the normal APRs group compared with the APR‐elevated groups regardless of the baseline disease activity. However, in patients with baseline CDAI moderate to high disease activity, the normal APRs group less frequently required initiation of the biologic disease‐modifying anti‐rheumatic drugs compared with the APR‐elevated groups (P = 0.044).ConclusionActive RA patients with normal APR values have milder disease presentation, but similar clinical outcomes to those with elevated APRs.
Mind the Gap: Why Do Experts Have Differences of Opinion Regarding the Sufficiency of Audit Evidence Supporting Complex Fair Value Measurements?
Authors: Glover Steven M. , Taylor Mark H. , Wu Yi‐Jing , Trotman Ken T. 
Published: January 2019

ABSTRACTReported deficiencies continue to persist in audits of fair value measurements and other complex accounting estimates (hereafter, “FVMs”), despite improvements in auditor performance observed by regulators. The persistence of reported deficiencies in audits of FVMs suggests that factors underlying this trend may be more complicated and multidimensional than previously suggested by regulators and academic research, which has focused largely on auditors' unsatisfactory performance as the principal source of reported deficiencies. Drawing from the judgment and decision‐making expertise literature, we gather field‐based data from audit experts to identify additional factors that are likely to be contributing to differences of opinion between audit and inspection experts and the persistence of reported deficiencies in audits of FVMs. We find evidence that audit experts interpret standards and evaluate audit evidence differently than inspectors, and thus perceive there to be a gap between what auditors and inspectors regard as sufficient appropriate audit evidence to support audits of FVMs (hereafter, “FVM gap”). Moreover, results highlight several areas in audits of FVMs where differences of opinion exist between auditor and inspector experts regarding what constitutes a reported deficiency. Within the contexts we examine, our results identify additional factors, beyond deficient auditor performance, that may contribute to the FVM gap. We also report audit partners' recommendations for ways to reduce the FVM gap and suggest avenues for future research. Gaining a more complete understanding of sources contributing to reported deficiencies will help regulators, standard setters, audit firms, and academics to identify ways to reduce the FVM gap and reported deficiencies in audits of FVMs.
Gender Disparities in Alcohol Use Disorder Treatment Among Privately Insured Patients with Alcohol‐Associated Cirrhosis
Authors: Mellinger Jessica L. , Fernandez Anne , Shedden Kerby , Winder G. Scott , Fontana Robert J. , Volk Michael L. , Blow Frederic C. , Lok Anna S. F. 
Published: January 2019

BackgroundThe burden of alcohol‐associated cirrhosis (AC) is high, and though alcohol cessation improves mortality, many patients fail to engage in alcohol use disorder (AUD) treatment and continue drinking. Our aim was to determine rates, predictors, and outcomes of AUD treatment utilization in AC patients with private insurance.MethodsWe collected data from persons with AC (diagnosed by ICD‐9/ICD‐10 codes), aged 18 to 64 years, enrolled in the Truven MarketScan Commercial Claims and Encounters database (2009 to 2016). We determined rates and predictors of substance abuse treatment visits as well as rates of alcohol relapse prevention medication prescriptions, weighted to the national employer‐sponsored insured population. Effects of AUD treatment utilization on decompensation rates were calculated using proportional hazards regression with propensity score adjustment.ResultsA total of 66,053 AC patients were identified, 32% were female, and mean age at diagnosis was 54.5 years. About 72% had insurance coverage for substance abuse treatment. Overall, AUD treatment utilization rates were low, with only 10% receiving a face‐to‐face mental health or substance abuse visit and only 0.8% receiving a Food and Drug Administration (FDA)‐approved relapse prevention medication within 1 year of index diagnosis. Women were less likely to receive a face‐to‐face visit (hazard ratio [HR] 0.84,p < 0.001) or an FDA‐approved relapse prevention medication (0.89,p = 0.05) than men. AC patients who had a clinic visit for AUD treatment or used FDA‐approved relapse medication showed decreased risk of decompensation at 1 year (HR 0.85,p < 0.001 for either).ConclusionsAUD treatment utilization is associated with lower decompensation rates among privately insured patients with AC. Women were less likely to utilize AUD treatment visits. Efforts to reduce gender‐specific barriers to treatment are urgently needed to improve outcomes.
Challenges and adjustments in maintaining health and well‐being of older Asian immigrants in New Zealand: An integrative review
Authors: Montayre Jed , De‐Arth Jaden , Shrestha‐Ranjit Jagamaya , Neville Stephen , Holroyd Eleanor 
Published: January 2019

ObjectiveThere is a paucity of health‐related research on older Asian immigrants in New Zealand. The aim of this review was to critically examine literature on the health and well‐being of this population group.MethodsAn integrative literature review was conducted from December 2017 to February 2018. Online databases searched were Scopus, MEDLINE, CINAHL and the Australia/New Zealand Reference Centre.ResultsTwo themes were identified: Firstly, the “challenges stemming from an unfamiliar environment” faced by older Asian immigrants, and secondly, their “strategies for adjusting to a new home.” These themes suggested how participation in community and leisure activities, as well as adapting their outlook on life, contributed to these older migrants’ health and well‐being within a New Zealand context.ConclusionA multitude of challenges in maintaining health and well‐being confronted these older Asian immigrants; nevertheless, they created strategies to respond and positively influence their health following later‐life migration.
Neutralization of IL‐17 rescues amyloid‐β‐induced neuroinflammation and memory impairment
Authors: Cristiano Claudia , Volpicelli Floriana , Lippiello Pellegrino , Buono Benedetta , Raucci Federica , Piccolo Marialuisa , Iqbal Asif Jilani , Irace Carlo , Miniaci Maria Concetta , Perrone Capano Carla , Calignano Antonio , Mascolo Nicola , Maione Francesco 
Published: January 2019

Background and purposeAlzheimer's disease (AD) is a common neurodegenerative disease characterized by a neuroinflammatory state, and to date, there is no cure and its treatment represents a large unmet clinical need. The involvement of Th17 cells in the pathogenesis of AD‐related neuroinflammation has been reported in several studies. However, the role of the cytokine, IL‐17 has not been well addressed. Herein, we investigate the effects of IL‐17 neutralizing antibody (IL‐17Ab) injected by i.c.v. or intranasal (IN) routes on amyloid‐β (Aβ)‐induced neuroinflammation and memory impairment in mice.Experimental approachAβ1–42 was injected into cerebral ventricles of adult CD1 mice. These mice received IL‐17Ab via i.c.v. either at 1 h prior to Aβ1–42 injection or IN 5 and 12 days after Aβ1–42 injection. After 7 and 14 days of Aβ1–42 administration, we evaluated olfactory, spatial and working memory and performed biochemical analyses on whole brain and specific brain areas.Key resultsPretreatment with IL‐17Ab, given, i.c.v., markedly reduced Aβ1–42‐induced neurodegeneration, improved memory function, and prevented the increase of pro‐inflammatory mediators in a dose‐dependent manner at 7 and 14 days. Similarly, the double IN administration of IL‐17Ab after Aβ1–42 injection reduced neurodegeneration, memory decline, and the levels of proinflammatory mediators and cytokines.Conclusion and implicationsThese findings suggest that the IL‐17Ab reduced neuroinflammation and behavioural symptoms induced by Aβ. The efficacy of IL‐17Ab IN administration in reducing Aβ1–42 neurodegeneration points to a possible future therapeutic approach in patients with AD.Linked ArticlesThis article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc
Developmental Outcomes for Children at High Risk of Dyslexia and Children With Developmental Language Disorder
Authors: Snowling Margaret J. , Nash Hannah M. , Gooch Debbie C. , Hayiou‐Thomas Marianna E. , Hulme Charles ,   Wellcome Language and Reading Project Team
Published: January 2019

We followed children at family risk of dyslexia and children with preschool language difficulties from age 3½, comparing them with controls (N = 234). At age 8, children were classified as having dyslexia or Developmental Language Disorder (DLD) and compared at earlier time points with controls. Children with dyslexia have specific difficulties with phonology and emergent reading skills in the preschool period, whereas children with DLD, with or without dyslexia, show a wider range of impairments including significant problems with executive and motor tasks. For children with both dyslexia and DLD, difficulties with phonology are generally more severe than those observed in children with dyslexia or DLD alone. Findings confirm that poor phonology is the major cognitive risk factor for dyslexia.
Association between peripheral plasmablasts and postoperative exacerbation in patients with thymoma‐associated myasthenia gravis
Authors: Izaki Shoko , Tanaka Satoru , Oji Satoru , Kubota Akihiro , Fukaura Hikoaki , Nakayama Mitsuo , Nomura Kyoichi 
Published: January 2019

AbstractObjectiveThymoma‐associated myasthenia gravis (TAMG) is a type of myasthenia gravis (MG) that has a higher likelihood of worsening in comparison with non‐TAMG, and MG symptoms often worsen after thymectomy. We measured peripheral T/B lymphocyte subsets before and after thymectomy in TAMG patients, and investigated the relationships with the occurrence of postoperative exacerbation of MG symptoms.MethodsParticipants were 10 TAMG patients, 40 healthy controls and five other surgical control patients. Peripheral lymphocyte subsets were measured using FACS‐Canto flow cytometry before, and 1, 7, and 28 days after thymectomy in the TAMG, and before and 7 days after thymectomy in the other surgical control patients.ResultsNatural killer cells modestly decreased, and plasmablasts increased significantly (P = 0.005) after 7 days postoperatively in comparison with preoperative values. Conversely, no obvious changes were observed in plasmablasts or natural killer cells in T/B lymphocyte subsets. From evaluation of postoperative clinical course and plasmablasts, exacerbation of MG symptoms was observed between 2 and 3 weeks after thymectomy in five of 10 patients (50%) of TAMG. In these five patients, plasmablasts markedly increased after thymectomy in three patients, among whom two patients had originally shown high plasmablast levels before thymectomy. There were also two patients who exacerbated without changes in plasmablast levels.ConclusionsIn patients with exacerbation of neurological symptoms after thymectomy for TAMG, the plasmablast levels were originally high and/or became high postoperatively. Thus, elevated plasmablast levels could potentially be predictive of postoperative exacerbation of MG.
Macrolide derivatives reduce proinflammatory macrophage activation and macrophage‐mediated neurotoxicity
Authors: Zhang Bei , Kopper Timothy J. , Liu Xiaodong , Cui Zheng , Van Lanen Steven G. , Gensel John C. 
Published: January 2019

SummaryIntroductionAzithromycin (AZM) and other macrolide antibiotics are applied as immunomodulatory treatments for CNS disorders. The immunomodulatory and antibiotic properties of AZM are purportedly independent.AimsTo improve the efficacy and reduce antibiotic resistance risk of AZM‐based therapies, we evaluated the immunomodulatory and neuroprotective properties of novel AZM derivatives. We semisynthetically prepared derivatives by altering sugar moieties established as important for inhibiting bacterial protein synthesis. Bone marrow‐derived macrophages (BMDMs) were stimulated in vitro with proinflammatory, M1, stimuli (LPS + INF‐gamma) with and without derivative costimulation. Pro‐ and anti‐inflammatory cytokine production, IL‐12 and IL‐10, respectively, was quantified using ELISA. Neuron culture treatment with BMDM supernatant was used to assess derivative neuroprotective potential.ResultsAzithromycin and some derivatives increased IL‐10 and reduced IL‐12 production of M1 macrophages. IL‐10/IL‐12 cytokine shifts closely correlated with the ability of AZM and derivatives to mitigate macrophage neurotoxicity.ConclusionsSugar moieties that bind bacterial ribosomal complexes can be modified in a manner that retains AZM immunomodulation and neuroprotection. Since the effects of BMDMs in vitro are predictive of CNS macrophage responses, our results open new therapeutic avenues for managing maladaptive CNS inflammation and support utilization of IL‐10/12 cytokine profiles as indicators of macrophage polarization and neurotoxicity.
Negative regulation of glial Tim‐3 inhibits the secretion of inflammatory factors and modulates microglia to antiinflammatory phenotype after experimental intracerebral hemorrhage in rats
Authors: Chen Zhou‐Qing , Yu Hao , Li Hai‐Ying , Shen Hai‐Tao , Li Xiang , Zhang Ju‐Yi , Zhang Zhu‐Wei , Wang Zhong , Chen Gang 
Published: January 2019

SummaryAimsTo investigate the critical role of Tim‐3 in the polarization of microglia in intracerebral hemorrhage (ICH)‐induced secondary brain injury (SBI).MethodsAn in vivo ICH model was established by autologous whole blood injection into the right basal ganglia in rats. The primary cultured microglia were treated with oxygen‐hemoglobin (OxyHb) to mimic ICH in vitro. In this experiment, specific siRNA for Tim‐3 and recombinant human TIM‐3 were exploited both in vivo and in vitro.ResultsTim‐3 was increased in the brain after ICH, which mainly distributed in microglia, but not neurons and astrocytes. However, the blockade of Tim‐3 by siRNA markedly reduced secretion of inflammatory factors, neuronal degeneration, neuronal cell death, and brain edema. Meanwhile, downregulation of Tim‐3 promoted the transformation of microglia phenotype from M1 to M2 after ICH. Furthermore, upregulation of Tim‐3 can increase the interaction between Tim‐3 and Galectin‐9 (Gal‐9) and activate Toll‐like receptor 4 (TLR‐4) pathway after ICH. Increasing the expression of Tim‐3 may be related to the activation of HIF‐1α.ConclusionTim‐3 may be an important link between neuroinflammation and microglia polarization through Tim‐3/Gal‐9 and TLR‐4 signaling pathways which induced SBI after ICH.
A review of evidence about use and performance of species distribution modelling ensembles like BIOMOD
Authors: Hao Tianxiao , Elith Jane , Guillera‐Arroita Gurutzeta , Lahoz‐Monfort José J. 
Published: January 2019

AbstractAimThe idea of combining predictions from different models into an ensemble has gained considerable popularity in species distribution modelling, partly due to free and comprehensive software such as the R package BIOMOD. However, despite proliferation of ensemble models, we lack oversight of how and where they are used for modelling distributions, and how well they perform. Here, we present such an overview.LocationGlobal.MethodsSince BIOMOD is freely available and widely used by ensemble species distribution modellers, we focused on articles that apply BIOMOD, filtering the initial 852 papers identified in our structured literature search to a relevant final subset of 224 eligible peer‐reviewed journal articles.ResultsBIOMOD‐based ensembles are used across many taxa and locations, with terrestrial plants being the most represented group of species (n = 72) and Europe being the most represented continent (n = 106). These studies often focus on forecasting distributions in the future (n = 109), and commonly use presence‐only species data (n = 139) and climatic environmental predictors (n = 219). An average of six models are used in ensembles, and approximately half of ensembles weight contributions of models by their cross‐validation performance. However, discussion about choices made in the modelling process and unambiguous information on the performance of ensemble models versus individual models are limited. The use of independent data to validate model performance is particularly uncommon.Main conclusionsWe document the breadth of ensemble applications, but could not draw strong quantitative conclusions about the predictive performance of ensemble models, due to lack of unambiguous information reported. Understanding how and where ensembles are best used when modelling species distributions is important for enabling best choices for different applications. To enable this objective to be achieved, we provide recommendations for thorough reporting practices in a BIOMOD‐based ensemble workflow.
Efficacy and safety of 0.6% sodium alginate solution in endoscopic submucosal dissection for esophageal and gastric neoplastic lesion: A randomized controlled study
Authors: Uemura Naomi , Oda Ichiro , Saito Yutaka , Ono Hiroyuki , Fujisaki Junko , Matsuhashi Nobuyuki , Ohata Ken , Yahagi Naohisa , Yada Tomoyuki , Satoh Masahiro , Tajiri Hisao , Inomata Masafumi , Kitano Seigo 
Published: January 2019

ObjectivesSodium alginate (SA) solution has characteristic viscoelasticity. We aimed to determine efficacy and safety of 0.6% SA for submucosal injection during endoscopic submucosal dissection (ESD) in patients with localized neoplastic lesion in the esophageal and gastric mucosa.MethodsWe conducted a randomized controlled study at six major hospitals in Japan including 130 patients with endoscopically localized neoplastic lesion in the esophageal and gastric mucosa and eligible for ESD. Patients were randomly assigned to SA or 0.4% sodium hyaluronate (SH) group (control); ESD was performed using a submucosal injection of SA/SH. As a primary outcome measure, non‐inferiority of SA against SH was investigated using en bloc complete resection in ESD and formation and maintenance of mucosal elevation upon injection as an efficacy index. Adverse events during the study were evaluated as safety outcome measures. This study was registered with Pharmaceuticals and Medical Devices Agency (clinical trial no. 28‐277/2016‐18; clinical trial identification no. KP2013‐009_C001).ResultsEfficacy rate of submucosal injection during ESD was 91.7% (55/60) and 88.7% (55/62) in the SA and SH groups, respectively, demonstrating non‐inferiority of SA against SH. Adverse events for which a causal relationship with submucosal injection solution could not be eliminated were noted in 8.2% (5/61) and 4.7% (3/64) in the SA and SH groups, respectively, but symptoms disappeared without treatment/after drug administration in both groups.ConclusionsIn Japan, 0.4% SH is the only commercially approved formulation for submucosal injection during ESD. The study results may expand submucosal injection solution options in clinical practice.
Environmental influences on health and development: nutrition, substance exposure, and adverse childhood experiences
Authors: Gentner Maura B , Leppert Mary L O’Connor 
Published: January 2019

Scientific advances over the last century have generated compelling evidence of the primary and secondary effects of gestational, infant, and childhood conditions. These early environmental influences have the potential not only to impact an individual's health outcomes, such as heart disease, type 2 diabetes, and cancer, but also to confer various protections and risks to that individual's descendants. The immediate and extended ramifications of early environmental exposure bring an understanding of epidemiological impact on disease states and a hope for prevention. This review highlights the contributions of several key population studies and briefly explores specific environmental influences, including nutritional deficiencies, exposure to substances and infections, and adverse childhood experiences. Mechanisms of these influences (e.g. stress and epigenetics) are discussed, as well as possible means of mitigating their negative consequences.What this paper adds

Substance exposures in utero are associated with epigenetic changes and negative outcomes.

Adverse childhood experiences in early childhood can induce HPA and epigenetic changes.
Metformin use and cardiovascular events in patients with type 2 diabetes and chronic kidney disease
Authors: Charytan David M. , Solomon Scott D. , Ivanovich Peter , Remuzzi Giuseppe , Cooper Mark E. , McGill Janet B. , Parving Hans‐Henrik , Parfrey Patrick , Singh Ajay K. , Burdmann Emmanuel A. , Levey Andrew S. , Eckardt Kai‐Uwe , McMurray John J.V. , Weinrauch Larry A. , Liu Jiankang , Claggett Brian , Lewis Eldrin F. , Pfeffer Marc A. 
Published: January 2019

AimsMetformin could have benefits on cardiovascular disease and kidney disease progression but is often withheld from individuals with diabetes and chronic kidney disease (CKD) because of a concern that it may increase the risk of lactic acidosis.Materials and methodsAll‐cause mortality, cardiovascular death, cardiovascular events (death, hospitalization for heart failure, myocardial infarction, stroke or myocardial ischemia), end stage renal disease (ESRD) and the kidney disease composite (ESRD or death) were compared in metformin users and non‐users with diabetes and CKD enrolled in the Trial to Reduce Cardiovascular Events with Aranesp (darbepoeitin‐alfa) Therapy (TREAT) (NCT00093015). Outcomes were compared after propensity matching of users and non‐users and in multivariable proportional hazards models.ResultsThere were 591 individuals who used metformin at baseline and 3447 non‐users. Among propensity‐matched users, the crude incidence rate for mortality, cardiovascular mortality, cardiovascular events and the combined endpoint was lower in metformin users than in non‐users, but ESRD was marginally higher (4.0% vs 3.6%). Metformin use was independently associated with a reduced risk of all‐cause mortality (HR, 0.49; 95% CI, 0.36‐0.69), cardiovascular death (HR, 0.49; 95% CI, 0.32‐0.74), the cardiovascular composite (HR, 0.67, 95% CI, 0.51‐0.88) and the kidney disease composite (HR, 0.77; 95% CI, 0.61‐0.98). Associations with ESRD (HR, 1.01; 95% CI, 0.65‐1.55) were not significant. Results were qualitatively similar in adjusted analyses of the full population. Two cases of lactic acidosis were observed.ConclusionsMetformin may be safer for use in CKD than previously considered and may lower the risk of death and cardiovascular events in individuals with stage 3 CKD.