bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pro‐gastrin‐releasing peptide and outcome in patients with heart failure and anaemia: results from the RED‐HF study
Authors: Ueland Thor , Gullestad Lars , Kou Lei , Aukrust Pål , Anand Inderjit S. , Broughton Marianne Nordlund , McMurray John J. , van Veldhuisen Dirk J. , Warren David J. , Bolstad Nils 
Published: August 2018

AbstractAimsNeuroendocrine activation is associated with poor outcome in heart failure (HF). The neuropeptide gastrin‐releasing peptide (GRP), derived from the precursor proGRP1‐125 (proGRP), has recently been implicated in inflammation and wound repair. We investigated the predictive value of proGRP on clinical outcomes in HF patients with reduced ejection fraction.Methods and resultsThe association between plasma proGRP (time‐resolved immunofluorometric assay) and the primary endpoint of death from any cause or first hospitalization for worsening of HF was evaluated using multivariable Cox proportional hazard models in 1541 patients with systolic HF and mild to moderate anaemia, enrolled in the Reduction of Events by Darbepoetin alfa in Heart Failure (RED‐HF) trial. Median proGRP levels in the RED‐HF cohort were markedly increased [95 ng/L (25th, 75th percentile, 69–129 ng/L)] with 64% patients above the 80 ng/L reference limit. Baseline proGRP correlated with estimated glomerular filtration rate (r = 0.52), N terminal pro brain natriuretic peptide (r = 0.33), troponin T (r = 0.34), and haemoglobin (r = 0.16) (all P < 0.001). The incidence outcome increased with increasing tertiles of baseline proGRP (primary endpoint third tertile vs. the lowest tertile; hazard ratio 1.91; 95% confidence interval 1.60–2.28, P < 0.001). However, these associations were markedly attenuated and non‐significant in adjusted models. No interaction between baseline proGRP and the effect of darbepoetin alfa treatment was detected. Moreover, no significant association between changes in proGRP during 6 month follow‐up and outcome was observed.ConclusionsPro‐gastrin‐releasing peptide is increased in patients with HF with reduced ejection fraction and anaemia, in particular in patients with poor renal function. However, proGRP adds little as a prognostic marker on top of conventional HF risk factors.
Pharmacoproteomics Profiling of Plasma From β‐Thalassemia Patients in Response to Hydroxyurea Treatment
Authors: Zohaib Muhammad , Ansari Saqib H. , Shamsi Tahir S. , Zubarev Roman A. , Zarina Shamshad 
Published: August 2018

Abstractβ‐Thalassemia is a genetic disorder caused by defects in the β‐globin gene resulting in the absence or reduced synthesis of adult hemoglobin (HbA). Hydroxyurea is an effective drug to increase fetal γ‐globin (HbF) expression, replacing the missing adult β‐globin. The mechanism of HbF induction by hydroxyurea and improvement in clinical symptoms are still poorly understood. In the present study we performed comparative analysis of plasma proteome in pre– and post–hydroxyurea‐treated β‐thalassemia major transfusion‐dependent children (n = 10, mean age = 3.2 years) as well as responders versus nonresponders to hydroxyurea treatment. Plasma was collected before and after 6 months of hydroxyurea treatment, with patients subcategorized on the basis of their response to hydroxyurea. Among 400 identified proteins using a label‐free quantitative proteomics approach, 28 proteins were found to be significantly different in pre– versus post–hydroxyurea‐treated groups, with transferrin receptor protein‐1 being most downregulated and hemopexin and haptoglobin the most upregulated proteins after treatment. In responder versus nonresponder comparison, 26 proteins were found to be differentially expressed, with carbonic anhydrase 1, hemoglobin subunit γ‐1, and peroxiredoxin‐2 showing the significant changes. The mechanism of hydroxyurea treatment in β‐thalassemia patients appears to be complex, requiring a large sample size and a longer period of treatment to reveal its details.
Value of MRI in medicine: More than just another test?
Authors: van Beek Edwin J.R. , Kuhl Christiane , Anzai Yoshimi , Desmond Patricia , Ehman Richard L. , Gong Qiyong , Gold Garry , Gulani Vikas , Hall‐Craggs Margaret , Leiner Tim , Lim C.C. Tschoyoson , Pipe James G. , Reeder Scott , Reinhold Caroline , Smits Marion , Sodickson Daniel K. , Tempany Clare , Vargas H. Alberto , Wang Meiyun 
Published: August 2018

There is increasing scrutiny from healthcare organizations towards the utility and associated costs of imaging. MRI has traditionally been used as a high‐end modality, and although shown extremely important for many types of clinical scenarios, it has been suggested as too expensive by some. This editorial will try and explain how value should be addressed and gives some insights and practical examples of how value of MRI can be increased. It requires a global effort to increase accessibility, value for money, and impact on patient management. We hope this editorial sheds some light and gives some indications of where the field may wish to address some of its research to proactively demonstrate the value of MRI.Level of Evidence: 5Technical Efficacy: Stage 5J. Magn. Reson. Imaging 2019;49:e14–e25.
Olfactory implant: Demand for a future treatment option in patients with olfactory dysfunction
Authors: Besser Gerold , Liu David T. , Renner Bertold , Hummel Thomas , Mueller Christian A. 
Published: August 2018

ObjectivesTherapeutic options in olfactory dysfunction (OD) are limited. Numerous studies have shown impact of OD on quality of life. Lately, various studies support benefits of olfactory training, but therapy‐refractory cases leave doctors and patients locked in a stalemate. An olfactory implant (OI), in analogy to the widely successful cochlear implant, still seems far away from realization. The present study sought to evaluate the demand of OI in patients with OD.MethodsSixty‐one patients (28 females and 33 males, mean age/standard deviation 54.9/17.6 years) with OD were recruited. We performed olfactory testing for threshold (T), discrimination (D), and identification (I) using Sniffin' Sticks; summed scores (TDI) allowed us to determine normosmia, hyposmia, and anosmia. We applied questionnaires on the importance of smell (IOS), on olfactory disorders (QOD) and on the interest/willingness for OI, considering the need for skull base/head surgery.ResultsTwenty‐one patients (34.4%) stated that OI could be a future treatment option for them. This decision significantly correlated with TDI, I, complaint‐related questions of the QOD, and IOS (P < .05).ConclusionWith approximately one‐third of patients considering OI as a therapy option, this study seems to indicate a demand for OI. In selected patients, with a high degree of complaints, low olfactory test scores, and maybe an additional occupational need for olfactory function, OI might be an option if future developments warrant safety of OI procedures.Level of Evidence4 Laryngoscope, 129:312–316, 2019
The iron limitation mosaic in the California Current System: Factors governing Fe availability in the shelf/near‐shelf region
Authors: Till C. P. , Solomon J. R. , Cohen N. R. , Lampe R. H. , Marchetti A. , Coale T. H. , Bruland K. W. 
Published: August 2018

AbstractThe California Current System is a productive eastern boundary region off the coasts of Washington, Oregon, and California. There is strong seasonality to the region, with high levels of rainfall and river input to the coastal ocean during the winter season, and coastal and Ekman upwelling during the spring and summer. Iron (Fe) input to the coastal ocean during the winter months can be stored in the continental shelf mud belts and then be delivered to the surface ocean by upwelling in the spring and summer. There have been a number of studies providing strong evidence of Fe‐limitation of diatom growth occurring in regions of the California Current System off of California, and the occurrence of Fe‐limitation has been linked with narrow continental shelf mud belt width and low river input. We provide evidence for potential Fe‐limitation of diatoms off the southern coast of Oregon in July 2014, just off the shelf break near Cape Blanco in a region with moderate shelf width and river input. Since eastern boundary regions account for a disproportionally large amount of global primary production, this observation of potential Fe‐limitation in an unexpected near‐shore region of the California Current System has implications for global models of primary productivity. In order to re‐evaluate the factors impacting Fe availability, we utilize satellite imagery to compare with historical datasets, and show that unexpected levels of Fe can often be explained by eddies, plumes of upwelled water moving offshore, or lack of recent upwelling.
Validation of the MDS clinical diagnostic criteria for Parkinson's disease
Authors: Postuma Ronald B. , Poewe Werner , Litvan Irene , Lewis Simon , Lang Anthony E. , Halliday Glenda , Goetz Christopher G. , Chan Piu , Slow Elizabeth , Seppi Klaus , Schaffer Eva , Rios‐Romenets Silvia , Mi Taomian , Maetzler Corina , Li Yuan , Heim Beatrice , Bledsoe Ian O. , Berg Daniela 
Published: August 2018

AbstractBackground: In 2015, the International Parkinson and Movement Disorder Society published clinical diagnostic criteria for Parkinson's disease. These criteria aimed to codify/reproduce the expert clinical diagnostic process and to help standardize diagnosis in research and clinical settings. Their accuracy compared with expert clinical diagnosis has not been tested. The objectives of this study were to validate the International Parkinson and Movement Disorder Society diagnostic criteria against a gold standard of expert clinical diagnosis, and to compare concordance/accuracy of the International Parkinson and Movement Disorder Society criteria to 1988 United Kingdom Brain Bank criteria.Methods: From 8 centers, we recruited 626 parkinsonism patients (434 PD, 192 non‐PD). An expert neurologist diagnosed each patient as having PD or non‐PD, regardless of International Parkinson and Movement Disorder Society criteria (gold standard, clinical diagnosis). Then a second neurologist evaluated the presence/absence of each individual item from the International Parkinson and Movement Disorder Society criteria. The overall accuracy/concordance rate, sensitivity, and specificity of the International Parkinson and Movement Disorder Society criteria compared with the expert gold standard were calculated.Results: Of 434 patients diagnosed with PD, 94.5% met the International Parkinson and Movement Disorder Society criteria for probable PD (5.5% false‐negative rate). Of 192 non‐PD patients, 88.5% were identified as non‐PD by the criteria (11.5% false‐positive rate). The overall accuracy for probable PD was 92.6%. In addition, 59.3% of PD patients and only 1.6% of non‐PD patients met the International Parkinson and Movement Disorder Society criteria for clinically established PD. In comparison, United Kingdom Brain Bank criteria had lower sensitivity (89.2%, P = 0.008), specificity (79.2%, P = 0.018), and overall accuracy (86.4%, P < 0.001). Diagnostic accuracy did not differ according to age or sex. Specificity improved as disease duration increased.Conclusions: The International Parkinson and Movement Disorder Society criteria demonstrated high sensitivity and specificity compared with the gold standard, expert diagnosis, with sensitivity and specificity both higher than United Kingdom Brain Bank criteria. © 2018 International Parkinson and Movement Disorder Society
Harnessing the power of placebos in movement disorders: Insights from Parkinson's disease in clinical research and practice
Authors: Mestre Tiago A. , Shamy Michel , Benedetti Fabrizio , Lang Anthony E. 
Published: August 2018

ABSTRACTThe placebo effect alongside the detrimental nocebo and lessebo effects associated with the use of placebos are well‐recognized phenomena. Research conducted in the last two decades has demonstrated that the placebo effect is a measurable health benefit with well‐known neurobiological correlates. In this review, we describe the current knowledge about how to best make use of the placebo effect to improve clinical research and optimize clinical care. We will cover four key topics: (1) setting the stage: historical perspectives on the use of placebos; (2) optimizing the use of placebos in clinical trials; (3) use of placebos in clinical practice; and (4) how can we minimize the ethical risks of using placebos? The adoption of the placebo‐controlled trial as a standard in the therapeutic development reduced the placebo effect to background noise in a therapeutic signal. Strategies to minimize the placebo effect in clinical trials have been used to obtain positive efficacy results. In more recent years, new study paradigms encouraged a change in the views on placebos and the placebo effect. Alternative study designs and the development of biomarkers for a placebo response permit a better understanding of the contribution of the placebo effect to the results of interventional studies, without minimizing it. In clinical practice, optimizing the placebo effect (and reducing nocebo effects) has the potential to improve care for our patients, but raises ethical challenges. An enhanced patient‐physician relationship would be central to any evidence‐based intervention used in clinical care to heighten the placebo effect. © 2018 International Parkinson and Movement Disorder Society
Progressive myoclonus ataxia: Time for a new definition?
Authors: van der Veen Sterre , Zutt Rodi , Elting Jan Willem J. , Becker Charlotte E. , de Koning Tom J. , Tijssen Marina A.J. 
Published: August 2018

ABSTRACTBackground: The clinical demarcation of the syndrome progressive myoclonus ataxia is unclear, leading to a lack of recognition and difficult differentiation from other neurological syndromes.Objectives: The objective of this study was to apply a refined definition of progressive myoclonus ataxia and describe the clinical characteristics in patients with progressive myoclonus ataxia and with isolated cortical myoclonus.Methods: A retro‐ and prospective analysis was performed in our tertiary referral center between 1994 and 2014. Inclusion criteria for progressive myoclonus ataxia patients were the presence of myoclonus and ataxia with or without infrequent (all types, treatment responsive) epileptic seizures. Inclusion criteria for isolated cortical myoclonus was the presence of isolated cortical myoclonus. Clinical and electrophysiological characteristics data were systematically scored.Results: A total of 14 progressive myoclonus ataxia patients (males, 7; females, 7), median age 14.5 years, and 8 isolated cortical myoclonus patients (males, 2; females, 6), median age 23.5 years, were identified. In 93% of the progressive myoclonus ataxia patients, ataxia started first (median 2 years) followed by myoclonus (4 years) and finally infrequent epilepsy (9.3 years), with a progressive course in 93%. In 64% of the progressive myoclonus ataxia patients, a genetic underlying etiology was identified, including 3 not earlier reported causative progressive myoclonus ataxia genes. In isolated cortical myoclonus patients, myoclonus started at (median) 12 years with progression over time in 63% and a single epileptic seizure in 1 patient. No genetic causes were identified.Conclusion: Using a refined definition, we could create a rather homogenous progressive myoclonus ataxia group. Patients with isolated cortical myoclonus have a different course and do not appear to evolve in progressive myoclonus ataxia. The refined progressive myoclonus ataxia definition is a successful first step toward creating a separate syndrome for both clinical practice and future genetic research. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Higher serum cholesterol and decreased Parkinson's disease risk: A statin‐free cohort study
Authors: Rozani Violetta , Gurevich Tanya , Giladi Nir , El‐Ad Baruch , Tsamir Judith , Hemo Beatriz , Peretz Chava 
Published: August 2018

ABSTRACTBackground: Higher levels of serum cholesterol are well‐established risk factors for coronary artery disease and stroke. The role of serum cholesterol in neurodegeneration is not clear.Objective: We evaluated the association between serum cholesterol levels over time and the risk of Parkinson's disease (PD) among statin‐free individuals.Methods: A population‐based cohort study of 261,638 statin‐free individuals (aged 40‐79 years at their first serum cholesterol test, 42.7% men), with repeated measures of total, low, and high‐density lipoprotein cholesterol was performed from 1999 to 2012. Individuals were followed from their first cholesterol test until PD incidence, death, or end of study. The PD incidence was assessed using a validated antiparkinsonian‐drug tracing approach. Cox models stratified by sex and age with time‐dependent cholesterol variables were applied to estimate PD hazard ratios.Results: A total of 764 (3.3% patients aged 65 + years) incident PD cases were detected during a mean follow‐up of 7.9 (±3.6) years. Among men, the middle and upper tertiles of total and low‐density lipoprotein cholesterol compared to the lowest were significantly associated with a lower PD risk. Age‐pooled hazard ratios (95% confidence interval) for middle and upper tertiles were 0.82 (0.66‐1.01) and 0.71 (0.55‐0.93), respectively, for total cholesterol, and 0.80 (0.65‐0.98) and 0.72 (0.54‐0.95) respectively, for low‐density lipoprotein cholesterol. Among women, the association between total and low‐density lipoprotein cholesterol levels with PD risk was not significant. Null results were found for both sexes for high‐density lipoprotein cholesterol.Conclusions: Higher levels of total and low‐density lipoprotein cholesterol among men over time indicated a decreased PD risk. The potential role of cholesterol in disease protection warrants further investigation. © 2018 International Parkinson and Movement Disorder Society
Longer β oscillatory episodes reliably identify pathological subthalamic activity in Parkinsonism
Authors: Deffains Marc , Iskhakova Liliya , Katabi Shiran , Israel Zvi , Bergman Hagai 
Published: August 2018

ABSTRACTBackground: The efficacy of deep brain stimulation (DBS) ‐ primarily of the subthalamic nucleus (STN) ‐ for advanced Parkinson's disease (PD) is commonly attributed to the suppression of pathological synchronous β oscillations along the cortico‐thalamo‐basal ganglia network. Conventional continuous high‐frequency DBS indiscriminately influences pathological and normal neural activity. The DBS protocol would therefore be more effective if stimulation was only applied when necessary (closed‐loop adaptive DBS).Objectives and Methods: Our study aimed to identify a reliable biomarker of the pathological neuronal activity in parkinsonism that could be used as a trigger for adaptive DBS. To this end, we examined the oscillatory features of paired spiking activities recorded in three distinct nodes of the basal ganglia network of 2 African green monkeys before and after induction of parkinsonism (by MPTP intoxication).Results: Parkinsonism‐related basal ganglia β oscillations consisted of synchronized time‐limited episodes, rather than a continuous stretch, of β oscillatory activity. Episodic basal ganglia β oscillatory activity, although prolonged in parkinsonism, was not necessarily pathological given that short β episodes could also be detected in the healthy state. Importantly, prolongation of the basal ganglia β episodes was more pronounced than their intensification in the parkinsonian state—especially in the STN. Hence, deletion of longer β episodes was more effective than deletion of stronger β episodes in reducing parkinsonian STN synchronized oscillatory activity.Conclusions: Prolonged STN β episodes are pathological in parkinsonism and can be used as optimal trigger for future adaptive DBS applications. © 2018 International Parkinson and Movement Disorder Society
Movement disorder society criteria for clinically established early Parkinson's disease
Authors: Berg Daniela , Adler Charles H. , Bloem Bastiaan R. , Chan Piu , Gasser Thomas , Goetz Christopher G. , Halliday Glenda , Lang Anthony E. , Lewis Simon , Li Yuan , Liepelt‐Scarfone Inga , Litvan Irene , Marek Kenneth , Maetzler Corina , Mi Taomian , Obeso José , Oertel Wolfgang , Olanow C. Warren , Poewe Werner , Rios‐Romenets Silvia , Schäffer Eva , Seppi Klaus , Heim Beatrice , Slow Elizabeth , Stern Matthew , Bledsoe Ian O. , Deuschl Günther , Postuma Ronald B. 
Published: August 2018

ABSTRACTBackground: In 2015, the International Parkinson and Movement Disorder Society published clinical diagnostic criteria for Parkinson's disease (PD). Although recent validation studies suggest high accuracy, one unmet need is for highly specific criteria for clinical trials in early/de novo PD.Objectives: The objective of this study was to generate and test a PD diagnostic criteria termed “clinically established early PD.”Methods: We modified the Movement Disorder Society criteria to increase specificity for early PD by removing all disease duration components and changing red flags to absolute exclusions. We then estimated the sensitivity/specificity of clinically established early PD criteria in patients with disease duration <5 years, selected from a 626‐patient validation study.Results: After documentation of parkinsonism, 18 individual exclusion criteria are assessed that preclude the diagnosis of “clinically established early PD.” Among 212 PD and 152 non‐PD patients, the estimated specificity was 95.4%, with 69.8% sensitivity.Conclusions: We describe high‐specificity criteria for de novo PD, which are freely available for use in clinical trials. © 2018 International Parkinson and Movement Disorder Society
Occupational stress and risk for Parkinson's disease: A nationwide cohort study
Authors: Sieurin Johanna , Andel Ross , Tillander Annika , Valdes Elise G. , Pedersen Nancy L. , Wirdefeldt Karin 
Published: August 2018

ABSTRACTBackground: Stress has been suggested as a contributing factor in the etiology of Parkinson's Disease (PD), but epidemiological evidence is sparse.Objective: The objective of this study was to explore the association between occupational stress according to the job demands‐control model and the risk for PD.Methods: We conducted a population‐based cohort study with 2,544,748 Swedes born 1920 to 1950 who had an occupation reported in the population and housing censuses in 1980 or, if missing, in 1970. Job demands and control were measured using a job‐exposure matrix. Incident PD cases were identified using Swedish national health registers from 1987 to 2010. Data were analyzed with Cox regression with age as the underlying time scale, adjusting for sex, education, and chronic obstructive pulmonary disease as a proxy for smoking.Results: During a mean follow‐up time of 21.3 years, 21,544 incident PD cases were identified. High demands were associated with increased PD risk among men, most evident in men with high education. High control was associated with increased PD risk among the low educated. This association was more pronounced in women. High‐strain jobs (high demands and low control) was only associated with increased PDrisk among men with high education, whereas active jobs (high demands and high control) were associated with increased PD risk among men with low education.Interpretation: High job demands appear to increase PD risk in men, especially in men with high education, whereas high job control increases PD risk among low educated, more strongly in women. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.