bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sensitivity and Specificity of Diagnostic Criteria for Progressive Supranuclear Palsy
Authors: Ali Farwa , Martin Peter R. , Botha Hugo , Ahlskog J. Eric , Bower James H. , Masumoto Joseph Y. , Maraganore Demetrius , Hassan Anhar , Eggers Scott , Boeve Bradley F. , Knopman David S. , Drubach Daniel , Petersen Ronald C. , Dunkley Erika Driver , van Gerpen Jay , Uitti Ryan , Whitwell Jennifer L. , Dickson Dennis W. , Josephs Keith A. 
Published: February 2019

AbstractBackgroundIn 2017, the International Parkinson and Movement Disorder Society put forward new clinical criteria for the diagnosis of PSP, recognizing diverse PSP phenotypes. In this study, we compared the sensitivity and specificity of the new criteria with the National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy criteria at different times.MethodsPatients with clinical parkinsonism, clinical and/or neuropathological diagnosis of PSP, were identified from the Society for Progressive Supranuclear Palsy brain bank. All patients had neuropathologic diagnoses and detailed clinical examination performed by a neurologist at 1 of the 3 Mayo Clinic sites, in Florida, Arizona, and Minnesota. Clinical symptoms and signs were abstracted retrospectively in a blinded fashion and used to determine whether patients met either diagnostic criterion. Patients were divided into early and late disease stage groups using a 3‐year cutoff.ResultsA total of 129 patients were included, of whom 66 had PSP pathology (51%). The remainder had other neurodegenerative diseases. The overall sensitivity of the International Parkinson and Movement Disorder Society criteria was 87.9%, compared with 45.5% for the National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy criteria, whereas the specificity of the International Parkinson and Movement Disorder Society probable PSP criteria was 85.7%, compared with 90.5% for the National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy. Individual patients were noted to have features of multiple PSP phenotypes.ConclusionThe International Parkinson and Movement Disorder Society criteria recognize several phenotypes of progressive supranuclear palsy and hence have higher sensitivity than the previous criteria. © 2019 International Parkinson and Movement Disorder Society
Emerging links between pediatric lysosomal storage diseases and adult parkinsonism
Authors: Ysselstein Daniel , Shulman Joshua M. , Krainc Dimitri 
Published: February 2019

ABSTRACTLysosomal storage disorders comprise a clinically heterogeneous group of autosomal‐recessive or X‐linked genetic syndromes caused by disruption of lysosomal biogenesis or function resulting in accumulation of nondegraded substrates. Although lysosomal storage disorders are diagnosed predominantly in children, many show variable expressivity with clinical presentations possible later in life. Given the important role of lysosomes in neuronal homeostasis, neurological manifestations, including movement disorders, can accompany many lysosomal storage disorders. Over the last decade, evidence from genetics, clinical epidemiology, cell biology, and biochemistry have converged to implicate links between lysosomal storage disorders and adult‐onset movement disorders. The strongest evidence comes from mutations in Glucocerebrosidase, which cause Gaucher's disease and are among the most common and potent risk factors for PD. However, recently, many additional lysosomal storage disorder genes have been similarly implicated, including SMPD1, ATP13A2, GALC, and others. Examination of these links can offer insight into pathogenesis of PD and guide development of new therapeutic strategies. We systematically review the emerging genetic links between lysosomal storage disorders and PD. © 2019 International Parkinson and Movement Disorder Society
Exome sequencing in families with chronic central serous chorioretinopathy
Authors: Schellevis Rosa L. , van Dijk Elon H. C. , Breukink Myrte B. , Keunen Jan E. E. , Santen Gijs W. E. , Hoyng Carel B. , de Jong Eiko K. , Boon Camiel J. F. , den Hollander Anneke I. 
Published: February 2019

AbstractBackgroundCentral serous chorioretinopathy (CSC) is a chorioretinal disease characterized by fluid accumulation between the neuroretina and retinal pigment epithelium with unknown etiology. Family studies have suggested a heritable component for CSC with an autosomal dominant inheritance pattern. Therefore, exome sequencing was performed on familial cCSC to indentify the genetic components contributing to familial cCSC.MethodsExome sequencing was performed on 72 individuals of 18 families with CSC. In these families, we determined whether rare genetic variants (minor allele frequency < 1%) were segregated with CSC and also performed familial gene‐burden analysis.ResultsIn total, 11 variants segregated in two out of 18 families. One of these variants, c.4145C>T; p.T1382I (rs61758735) in the PTPRB gene, was also associated with CSC in a large case–control cohort sequenced previously (p = 0.009). Additionally, in 28 genes two or more different heterozygous variants segregated in two or more families, but no gene showed consistent associations in both the family gene‐burden results and gene‐burden analysis in the case–control cohort.ConclusionWe identified potential candidate genes for familial CSC and managed to exclude Mendelian inheritance of variants in one or a limited number of genes. Instead, familial CSC may be a heterogeneous Mendelian disease caused by variants in many different genes, or alternatively CSC may represent a complex disease to which both environmental factors and genetics contribute.
Identification of New Potent Acetylcholinesterase Inhibitors Using Virtual Screening and in vitro Approaches
Authors: Mokrani El Hassen , Bensegueni Abderrahmane , Chaput Ludovic , Beauvineau Claire , Djeghim Hanane , Mouawad Liliane 
Published: February 2019

AbstractAcetylcholinesterase (AChE) is currently the most favorable target for the symptomatic treatment and reduction of Alzheimer's disease (AD). In order to identify new potent inhibitors of this enzyme, we describe herein a new structure‐based virtual screening (SBVS) using the Institut Curie‐CNRS chemical library (ICCL), which contained at the screening date 14307 compounds. The strategy undertaken in this work consisted of the use of several docking programs in SBVS calculations followed by the application of a consensus method (vSDC) and a scrupulous visual analysis. It allowed us to obtain a high degree of success, with a yield of almost 86 %, since 12 hits were identified among only 14 molecules tested in vitro. Still more remarkably, 6 of these hits were more active than galantamine, the reference inhibitor. These hits were predicted to have good ADMET properties. The two most promising compounds can serve as leads for AD treatment.
Vegan and Animal Meal Composition and Timing Influence Glucose and Lipid Related Postprandial Metabolic Profiles
Authors: Draper Colleen Fogarty , Tini Giulia , Vassallo Irene , Godin Jean Philippe , Su MingMing , Jia Wei , Beaumont Maurice , Moco Sofia , Martin Francois‐Pierre 
Published: February 2019

ScopeFlexitarian dieting is increasingly associated with health benefits. The study of postprandial metabolic response to vegan and animal diets is essential to decipher how specific diet components may mediate metabolic changes.Methods and resultsA randomized, crossover, controlled vegan versus animal diet challenge is conducted on 21 healthy participants. Postprandial metabolic measurements are conducted at seven timepoints. Area under the curve analysis of the vegan diet response demonstrates higher glucose (EE 0.35), insulin (EE 0.38), triglycerides (EE 0.72), and nine amino acids at breakfast (EE 4.72–209.32); and six lower health‐promoting fatty acids at lunch (EE −0.1035 to −0.13) (p < 0.05).ConclusionsGlycemic and lipid parameters vary irrespective of diet type, demonstrating that vegan and animal meals contain health‐promoting and suboptimal nutrient combinations. The vegan breakfast produces the same pattern of elevated branched chain amino acids, insulin, and glucose as the animal diet from the fasting results, reflecting the low protein load in the animal and the higher branched‐chain amino acid load of the vegan breakfast. Liberalization of the vegan menu to vegetarian and the animal menu to a Nordic‐based diet can result in optimal metabolic signatures for both flexitarian diet strategies in future research.
Disentangling the Effects of Monounsaturated Fatty Acids from Other Components of a Mediterranean Diet on Serum Metabolite Profiles: A Randomized Fully Controlled Dietary Intervention in Healthy Subjects at Risk of the Metabolic Syndrome
Authors: Michielsen Charlotte C. J. R. , Hangelbroek Roland W.J. , Feskens Edith J. M. , Afman Lydia A. 
Published: February 2019

ScopeThe Mediterranean (MED) diet has been associated with a decreased risk of cardiovascular diseases. It is unclear whether this health effect can be mainly contributed to high intakes of monounsaturated fatty acids (MUFA), characteristic for the MED diet, or whether other components of a MED diet also play an important role.Methods and ResultsA randomized fully controlled parallel trial is performed to examine the effects of the consumption of a saturated fatty acid rich diet, a MUFA‐rich diet, or a MED diet for 8 weeks on metabolite profiles, in 47 subjects at risk of the metabolic syndrome. A total of 162 serum metabolites are assessed before and after the intervention by using a targeted NMR platform. Fifty‐two metabolites are changed during the intervention (false discovery rate [FDR]p < 0.05). Both the MUFA and MED diet decrease exactly the same fractions of LDL, including particle number, lipid, phospholipid, and free cholesterol fraction (FDRp < 0.05). The MED diet additionally decreases the larger subclasses of very‐low‐density lipoprotein (VLDL), related VLDL fractions, VLDL‐triglycerides, and serum‐triglycerides (FDRp < 0.05).ConclusionThe findings clearly demonstrate that the MUFA component is responsible for reducing LDL subclasses and fractions, and therefore causes an antiatherogenic lipid profile. Interestingly, consumption of the other components in the MED diet show additional health effects.
Exam‐level dose monitoring in CT: Quality metric consideration for multiple series acquisitions
Authors: Li Xinhua , Yang Kai , Liu Bob 
Published: February 2019

PurposeMulti‐series CT examination is common in the clinic, but no metric is agreed upon to report the overall dose from such an examination. This work proposes a relevant metric for tracking patient dose from multi‐series examinations and illustrates the evaluation method through explanatory examples.Materials and methodsIn each acquisition series, a previously reported method was used to evaluate the cross‐sectional average dose along the z‐axis of a water phantom, with inputs of CTDIvol, scan length, tube current, and patient water‐equivalent diameter. With a multi‐series examination, the dose at each z‐location was accumulated over all acquisition series. This method was applied to four clinical CT examinations. In three abdominal/pelvic examinations (patient weight, 107, 79, 79 kg), tube current modulation was applied in five acquisition series with scan lengths of 30–41.8 cm, while tube current was fixed in other series with short scan lengths (1.0, 7.9 cm). In another CT‐guided liver ablation procedure (patient weight, 114 kg), 22 series were acquired with constant mA and scan lengths of 1–30 cm. The maximum value of the overall dose profile of each examination was compared to five dose quantities, including CTDIvol,sum and SSDEsum by the ACR CT Dose Index Registry, scan length‐weighted CTDIvol and SSDE by a CT dose monitoring platform, and “max z location CTDIvol” by a CT manufacturer.ResultsA simple graphic display of dose as a function of the z‐axis location was presented for each acquisition series and for the whole examination. Differences up to 43.4% and 42.8%, or down to −93.5%, −93.5%, and −49.0%, were observed between the maximum value of the overall dose profile and five dose quantities (in the above order), respectively.ConclusionThe overall dose profile gives a complete description of z‐axis dose distribution for the studied CT examinations under a wide range of patient variables and acquisition conditions, including multiple acquisition series. Simple visualization of the doses across and beyond the scan ranges may provide a new tool for CT dose optimization.
The Effect of Medical Marijuana Laws on the Health and Labor Supply of Older Adults: Evidence from the Health and Retirement Study
Authors: Nicholas Lauren Hersch , Maclean Johanna Catherine 
Published: February 2019

AbstractOlder adults are at elevated risk of reducing labor supply due to poor health, partly because of high rates of symptoms that may be alleviated by medical marijuana. Yet, surprisingly little is known about how this group responds to medical marijuana laws (MMLs). We quantify the effects of state medical marijuana laws on the health and labor supply of adults age 51 and older, focusing on the 55 percent with one or more medical conditions with symptoms that may respond to medical marijuana. We use longitudinal data from the Health and Retirement Study to estimate event study and differences‐in‐differences regression models. Three principle findings emerge from our analysis. First, active state medical marijuana laws lead to lower pain and better self‐assessed health among older adults. Second, state medical marijuana laws lead to increases in older adult labor supply, with effects concentrated on the intensive margin. Third, the effects of MMLs are largest among older adults with a health condition that would qualify for legal medical marijuana use under current state laws. Findings highlight the role of health policy in supporting work among older adults and the importance of including older adults in assessments of state medical marijuana laws.
Bone marrow biopsy in the initial staging of Ewing sarcoma: Experience from a single institution
Authors: Cesari Marilena , Righi Alberto , Colangeli Marco , Gambarotti Marco , Spinnato Paolo , Ferraro Andrea , Longhi Alessandra , Abate Massimo Eraldo , Palmerini Emanuela , Paioli Anna , Ferrari Cristina , Donati Davide Maria , Picci Piero , Ferrari Stefano 
Published: February 2019

AbstractBackgroundEwing sarcoma (ES) is the second most common bone tumor in adolescents and children. Staging workup for ES includes imaging and bone marrow biopsy (BMB). The effective role of BMB is now under discussion.ProcedureA monoinstitutional retrospective analysis reviewed clinical charts, imaging, and histology of patients with diagnosis of ES treated at the Rizzoli Institute between 1998 and 2017.ResultsThe cohort included 504 cases of ES of bone; 137 (27%) had metastases at diagnosis, while the remaining 367 had localized disease. Twelve patients had a positive BMB (2.4%). Eleven had distant metastases detected at initial workup staging with imaging assessment: six patients presented with bone metastases, five with both bone and lung metastases. Only one patient with ES of the foot (second metatarsus) was found to have bone marrow involvement with negative imaging evaluation (0.3%).ConclusionsOn the basis of our data, we suggest reconsidering the effective role of BMB in initial staging workup for patients with ES with no signs of metastases by modern imaging techniques. In metastatic disease, the assessment of the bone marrow status may remain useful to identify a group of patients at very high risk who could benefit from different treatment strategies.
Results of a multicenter universal newborn screening program for sickle cell disease in Italy: A call to action
Authors: Colombatti Raffaella , Martella Maddalena , Cattaneo Laura , Viola Giampietro , Cappellari Anita , Bergamo Chiara , Azzena Silvia , Schiavon Sara , Baraldi Eugenio , Dalla Barba Beatrice , Trafojer Ursula , Corti Paola , Uggeri Marzia , Tagliabue Paolo Emilio , Zorloni Chiara , Bracchi Michela , Biondi Andrea , Basso Giuseppe , Masera Nicoletta , Sainati Laura 
Published: February 2019

AbstractBackgroundSickle cell disease (SCD) is a chronic multisystem disorder requiring comprehensive care that includes newborn screening (NBS) as the first step of care. Italy still lacks a national SCD NBS program and policy on blood disorders. Pilot single‐center screening programs and a regional targeted screening have been implemented so far, but more evidence is needed in order to impact health policies.Population and methodsNBS was offered to parents of newborns in gynecology clinics in Padova and Monza, tertiary care university hospitals in northern Italy. High‐performance liquid chromatography (HPLC) was performed as the first test on samples collected on Guthrie cards. Molecular analysis of the beta‐globin gene was performed on positive samples.ResultsA total of 5466 newborns were enrolled; for 5439, informed consents were obtained. A similar family origin was seen in the two centers (65% Italians, 9% mixed couples, 26% immigrants). Compared with SCD NBS programs in the United States and Europe, our results show a similar incidence of SCD patients and carriers. All SCD patients had a Sub‐Saharan family background; HbS carriers were 15% Caucasians (Italian, Albanians) and 10% from other areas (North Africa–India–South America); carriers of other hemoglobin variants were mainly (47%) from other areas.ConclusionsOur results demonstrate the feasibility of a multicentric NBS program for SCD, give information on HbS epidemiology in two Northern Italian Areas, and support previous European recommendation for a universal NBS program for SCD in Italy: a high incidence of patients and carriers has been detected, with a high percentage of Caucasian carriers, impossible to identify in a targeted NBS.
Variation of the prevalence of pediatric polypharmacy: A scoping review
Authors: Baker Courtney , Feinstein James A. , Ma Xuan , Bolen Shari , Dawson Neal V. , Golchin Negar , Horace Alexis , Kleinman Lawrence C. , Meropol Sharon B. , Pestana Knight Elia M. , Winterstein Almut G. , Bakaki Paul M. 
Published: February 2019

AbstractPurposeTo examine the range of prevalence of pediatric polypharmacy in literature through a scoping review, focusing on factors that contribute to its heterogeneity in order to improve the design and reporting of quality improvement, pharmacovigilance, and research studies.MethodsWe searched Ovid Medline, PubMed, EMBASE, CINAHL, Ovid PsycINFO, Cochrane CENTRAL, and Web of Science Core Collection databases for studies with concepts of children and polypharmacy, along with a hand search of the bibliographies of six reviews and 30 included studies. We extracted information regarding study design, disease conditions, and prevalence of polypharmacy.ResultsTwo hundred eighty‐four studies reported prevalence of polypharmacy. They were more likely to be conducted in North America (37.7%), published after 2010 (44.4%), cross‐sectional (67.3%), in outpatient settings (59.5%). Prevalence ranged from 0.9% to 98.4%, median 39.7% (interquartile range [IQR] 22.0%‐54.0%). Studies from Asia reported the highest median prevalence of 45.4% (IQR 27.3%‐61.0%) while studies from North America reported the lowest median prevalence of 30.4% (IQR 14.7%‐50.2%). Prevalence decreased over time: median 45.6% before 2001, 38.1% during 2001 to 2010, and 34% during 2011 to 2017. Studies involving children under 12 years had a higher median prevalence (46.9%) than adolescent studies (33.7%). Inpatient setting studies had a higher median prevalence (50.3%) than studies in outpatient settings (38.8%). Community level samples, higher number and duration of medications defining polypharmacy, and psychotropic medications were associated with lower prevalence.ConclusionsThe prevalence of pediatric polypharmacy is high and variable. Studies reporting pediatric polypharmacy should account for context, design, polypharmacy definition, and medications evaluated.
Effectiveness of Once/Day Dolutegravir Plus Boosted Darunavir as a Switch Strategy in Heavily Treated Patients with Human Immunodeficiency Virus
Authors: Navarro Jordi , Santos José Ramón , Silva Ana , Burgos Joaquin , Falcó Vicenç , Ribera Esteban , Imaz Arkaitz , Curran Adrian 
Published: February 2019

Study ObjectiveDual therapy with once/day dolutegravir (DTG) plus boosted darunavir (DRV/b) may be a suitable and effective strategy with a high genetic barrier to resistance in patients infected with human immunodeficiency virus (HIV). Our aim was to evaluate the effectiveness of DTG plus DRV/b (DTG+DRV/b) as a switch strategy in HIV‐infected patients, irrespective of their history of virologic failure (VF).DesignMulticenter retrospective cohort study.SettingHuman immunodeficiency outpatient treatment clinics at three university hospitals in Spain.PatientsFifty HIV‐infected adults who had a stable antiretroviral treatment (ART) regimen and an undetectable viral load for at least 6 months, and whose ART was switched to once/day DTG+DRV/b between January 2015 and January 2018 were included in the analysis. Historical genotype at the time of VF was available in 44 patients.Measurements and Main ResultsPatients were followed until VF or treatment discontinuation for any reason. The primary outcome was the percentage of patients with a viral load of 50 copies/mL or lower at the last follow‐up visit. Secondary outcomes included changes in CD4+ cell count, lipid profile, and renal function. Of the 50 patients included, median time of viral suppression was 52 months (interquartile range [IQR] 18–103 mo) and nadir CD4+ 89 cells/mm3 (IQR 37–241 cells/mm3). Patients had a history of a median of 8 ART combinations (IQR 4–11 combinations) and 3 VFs (IQR 2–8 VFs). The historical genotypes from 44 patients showed 41 patients (93.2%) with nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) resistance‐associated mutations (RAMs), 32 (72.7%) with nonnucleoside reverse transcriptase inhibitor (NNRTI) RAMs, and 12 (27.3%) with primary protease inhibitor (PI) RAMs; 7 (15.9%) had darunavir RAMs, and no patients had baseline integrase strand transfer inhibitor RAMs. Thirty‐seven patients (84.1%) had resistance to at least two antiretroviral classes. After a median of 25 months (IQR 17–28 mo) of follow‐up, 49 patients (98%) maintained a viral load of 50 copies/mL or lower, and 1 patient (2%) had VF. No new RAMs emerged at VF. At week 4, serum creatinine concentration increased a median of 0.12 mg/dl (0.03–0.23 mg/dl). At last visit, total cholesterol and low‐density lipoprotein cholesterol levels increased by a median of 9 mg/dl (IQR −18 to 40 mg/dl) and 16 mg/dl (IQR −9 to 40 mg/dl), respectively, whereas CD4+ cell count remained stable (median +13 cell/mm3).ConclusionIn this cohort of heavily treated HIV‐infected patients with virologic suppression, switching to the combination of DTG+DRV/b was a convenient regimen that was highly effective and had good tolerability.