bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rare Genetic Variant in SORL1 May Increase Penetrance of Alzheimer’s Disease in a Family with Several Generations of APOE-ɛ4 Homozygosity
Authors: Louwersheimer Eva , Cohn-Hokke Petra E. , Pijnenburg Yolande A.L. , Weiss Marjan M. , Sistermans Erik A. , Rozemuller Annemieke J. , Hulsman Marc , van Swieten John C. , van Duijn Cock M. , Barkhof Frederik , Koene Teddy , Scheltens Philip , Van der Flier Wiesje M. , Holstege Henne 
Published: November 2016

Background: The major genetic risk factor for late onset Alzheimer’s disease (AD) is the APOE- ɛ4 allele. However, APOE- ɛ4 homozygosity is not fully penetrant, suggesting co-occurrence of additional genetic variants. Objective: To identify genetic factors that, next to APOE- ɛ4 homozygosity, contribute to the development of AD. Methods: We identified a family with nine AD patients spanning four generations, with an inheritance pattern suggestive of autosomal dominant AD, with no variants in PSEN1, PSEN2, or APP. We collected DNA from four affected and seven unaffected family members and performed exome sequencing on DNA from three affected and one unaffected family members. Results: All affected family members were homozygous for the APOE- ɛ4 allele. Statistical analysis revealed that AD onset in this family was significantly earlier than could be expected based on APOE genotype and gender. Next to APOE- ɛ4 homozygosity, we found that all four affected family members carried a rare variant in the VPS10 domain of the SORL1 gene, associated with AβPP processing and AD risk. Furthermore, three of four affected family members carried a rare variant in the TSHZ3 gene, also associated with AβPP processing. Affected family members presented between 61 and 74 years, with variable presence of microbleeds/cerebral amyloid angiopathy and electroencephalographic abnormalities. Conclusion: We hypothesize that next to APOE- ɛ4 homozygosity, impaired SORL1 protein function, and possibly impaired TSHZ3 function, further disturbed Aβ processing. The convergence of these genetic factors over several generations might clarify the increased AD penetrance and the autosomal dominant-like inheritance pattern of AD as observed in this family.
Deleterious Effect of Butyrylcholinesterase K-Variant in Donepezil Treatment of Mild Cognitive Impairment
Authors: Sokolow Sophie , Li Xiaohui , Chen Lucia , Taylor Kent D. , Rotter Jerome I. , Rissman Robert A. , Aisen Paul S. , Apostolova Liana G. 
Published: November 2016

Background: Donepezil is an acetylcholinesterase inhibitor frequently prescribed for the treatment of mild cognitive impairment (MCI) though not approved by the Food and Drug Administration for this indication. In Alzheimer’s disease, butyrylcholinesterase (BChE) activity increases with disease progression and may replace acetylcholinesterase function. The most frequent polymorphism of BChE is the K-variant, which is associated with lower acetylcholine-hydrolyzing activity. BChE-K polymorphism has been studied in Alzheimer’s disease progression and donepezil therapy, and has led to contradictory results. Objectives: To determine whether BChE-K genotype predicts response to donepezil in MCI. Methods: We examined the association between BChE-K genotype and changes in cognitive function using the data collected during the ADCS vitamin E/donepezil clinical trial in MCI. Results: We found significant interactions between BChE-K genotype and the duration of donepezil treatment, with increased changes in MMSE and CDR-SB scores compared to the common allele in MCI subjects treated during the 3-year trial. We found faster MMSE decline and CDR-SB rise in BChE-K homozygous individuals treated with donepezil compared to the untreated. We observed similar interactions between BChE-K genotype and steeper changes in MMSE and CDR-SB scores in APOE4 carriers treated with donepezil compared to controls. Conclusion: BChE-K polymorphisms are associated with deleterious changes in cognitive decline in MCI patients treated with donepezil for 3 years. This indicates that BChE-K genotyping should be performed to help identify subsets of subjects at risk for donepezil therapy, like those carrying APOE4. BChE-K and APOE4 carriers should not be prescribed off-label donepezil therapy for MCI management.
Screening for Mild Cognitive Impairment and Dementia with Automated, Anonymous Online and Telephone Cognitive Self-Tests
Authors: Van Mierlo Lisa D. , Wouters Hans , Sikkes Sietske A.M. , Van der Flier Wiesje M. , Prins Niels D. , Bremer Jonne A.E. , Koene Teddy , Van Hout Hein P.J. 
Published: November 2016

Background: Many older people worry about cognitive decline. Early cognitive screening in an anonymous and easily accessible manner may reassure older people who are unnecessarily worried about normal cognitive aging while it may also expedite help seeking in case of suspicious cognitive decline. Objective: To develop and validate online and telephone-based automated self-tests of cognitive function. Methods: We examined the feasibility and validity of the self-tests in a prospective study of 117 participants of whom 34 had subjective cognitive decline (SCD), 30 had mild cognitive impairment (MCI), and 53 had dementia. The ability of these self-tests to accurately distinguish MCI and dementia from SCD was examined with ROC curves. Convergent validity was examined by calculating rank correlations between the self-tests and neuropsychological tests. Results: Both the online and telephone cognitive self-tests were feasible, because the majority of participants (86% and 80%, respectively) were able to complete them. The online self-test had adequate diagnostic accuracy in the screening for MCI and dementia versus SCD with an Area under the Curve (AUC) of 0.86 (95% CI: 0.78–0.93). The AUC of the MMSE was 0.82 (95% CI: 0.74–0.89). By contrast, the telephone self-test had lower diagnostic accuracy (AUC = 0.75, 95% CI: 0.64–0.86). Both self-tests had good convergent validity as demonstrated by moderate to strong rank correlations with neuropsychological tests. Conclusion: We demonstrated good diagnostic accuracy and convergent validity for the online self-test of cognitive function. It is therefore a promising tool in the screening for MCI and dementia.
Sample Size Estimation for Alzheimer’s Disease Trials from Japanese ADNI Serial Magnetic Resonance Imaging
Authors: Fujishima Motonobu , Kawaguchi Atsushi , Maikusa Norihide , Kuwano Ryozo , Iwatsubo Takeshi , Matsuda Hiroshi ,   for the Japanese Alzheimer’s Disease Neuroimaging Initiative (ADNI),   the Japanese Alzheimer’s Disease Neuroimaging Initiative (J-ADNI)
Published: November 2016

Background: Little is known about the sample sizes required for clinical trials of Alzheimer’s disease (AD)-modifying treatments using atrophy measures from serial brain magnetic resonance imaging (MRI) in the Japanese population. Objective: The primary objective of the present study was to estimate how large a sample size would be needed for future clinical trials for AD-modifying treatments in Japan using atrophy measures of the brain as a surrogate biomarker. Methods: Sample sizes were estimated from the rates of change of the whole brain and hippocampus by the k-means normalized boundary shift integral (KN-BSI) and cognitive measures using the data of 537 Japanese Alzheimer’s Neuroimaging Initiative (J-ADNI) participants with a linear mixed-effects model. We also examined the potential use of ApoE status as a trial enrichment strategy. Results: The hippocampal atrophy rate required smaller sample sizes than cognitive measures of AD and mild cognitive impairment (MCI). Inclusion of ApoE status reduced sample sizes for AD and MCI patients in the atrophy measures. Conclusion: These results show the potential use of longitudinal hippocampal atrophy measurement using automated image analysis as a progression biomarker and ApoE status as a trial enrichment strategy in a clinical trial of AD-modifying treatment in Japanese people.
Association between Cognitive Status before Surgery and Outcomes in Elderly Patients with Hip Fracture in a Dedicated Orthogeriatric Care Pathway
Authors: Zerah Lorene , Cohen-Bittan Judith , Raux Mathieu , Meziere Anthony , Tourette Cendrine , Neri Christian , Verny Marc , Riou Bruno , Khiami Frederic , Boddaert Jacques 
Published: November 2016

Background: Dementia is associated with a worse prognosis of hip fracture, but the impact of a dedicated geriatric care pathway on the prognosis of these patients has not been evaluated. Objective: According to the cognitive status before surgery, our main objective was to compare mortality rate at 6 months; secondary outcomes were to compare in-hospital complications, the risk of new institutionalization, and the ability to walk at 6 months. Methods: Between 2009 and 2015, all patients (>70 years) admitted after hip fracture surgery into a dedicated unit of peri-operative geriatric care were included: patients with dementia (DP), without dementia (NDP), and with cognitive status not determined (CSND). Data are expressed as hazard ratio (HR) for multivariate cox analysis or odds ratio (OR) for multivariate logistic regression analysis and their 95% confidence interval (CI). Results: We included 650 patients (86±6 years): 168 DP, 400 NDP, and 82 CSND. After adjustment for age, sex, comorbidities, polypharmacy, pre-fracture autonomy, time-to-surgery, and delirium, there were no significant differences for 6-month mortality (DP versus NDP: HR = 0.7[0.4–1.2], DP versus CSND: HR = 0.6[0.3–1.4], CSND versus NDP: HR = 0.8[0.4–1.7]); but DP and CSND were more likely to be newly institutionalized after 6 months compared to NDP (OR DP = 2.6[1.4–4.9], p = 0.003, OR CSND = 2.9[1.4–6.1], p = 0.004). 92% of population was walking after 6 months (63% with assistance): no difference was found between the three groups. Conclusion: In a dedicated geriatric care pathway, DP and CSND undergoing hip surgery have the same 6-month mortality and walking ability as NDP.
Challenges in Screening and Recruitment for a Neuroimaging Study in Cognitively Impaired Geriatric Inpatients
Authors: Apostolova Ivayla , Lange Catharina , Roberts Anna , Igel Hans Joachim , Mäurer Anja , Liese Stephanie , Estrella Melanie , Prasad Vikas , Stechl Elisabeth , Lämmler Gernot , Steinhagen-Thiessen Elisabeth , Buchert Ralph 
Published: November 2016

Background: Neuroimaging-based biomarkers have the potential to improve etiological diagnosis of cognitive impairment in elderly inpatients. However, there is a relative lack of studies on neuroimaging-based biomarkers in hospitalized geriatric patients, as the vast majority of neuroimaging studies in dementia have focused on memory clinic outpatients. An important aspect of study planning is a priori estimation of the rate of screen failures. Objective: To report on the rate and causes of screen failures in a prospective study on the utility of neuroimaging (PET, MRI) for the etiological diagnosis of newly manifested cognitive impairment in acutely hospitalized geriatric patients. Methods: Ten acute care geriatrics clinics with 802 beds participated in the study. The potential recruitment rate had been estimated to 5 patients/100 beds/week. Results: Seventeen months of pre-screening resulted in 322 potential participants. 109 of these patients were enrolled, i.e., the screen failure rate was 66%. 58% of the screen failures were due to refusal of participation by the patient, most often due to lack of interest in clarifying the cause of the cognitive impairment or due to reluctance to engage in additional diagnostic procedures associated with physical stress. 42% of pre-screened patients were excluded because of violation of the eligibility criteria. Conclusion: Enrollment for neuroimaging studies presents considerable additional challenges in acutely hospitalized geriatric patients compared to outpatient settings. Low rate of approaching potential candidates by attending geriatricians and a high rate of screen failures have to be anticipated in the study design.
Ethnic Variations in Prognosis of Patients with Dementia: A Prospective Nationwide Registry Linkage Study in The Netherlands
Authors: Agyemang Charles , van de Vorst Irene E. , Koek Huiberdina L. , Bots Michiel L. , Seixas Azizi , Norredam Marie , Ikram Umar , Stronks Karien , Vaartjes Ilonca 
Published: November 2016

Background: Data on dementia prognosis among ethnic minority groups are limited in Europe. Objective: We assessed differences in short-term (1-year) and long-term (3-year) mortality and readmission risk after a first hospitalization or first ever referral to a day clinic for dementia between ethnic minority groups and the ethnic Dutch population in the Netherlands Methods: Nationwide prospective cohorts of first hospitalized dementia patients (N = 55,827) from January 1, 2000 to December 31, 2010 were constructed. Differences in short-term and long-term mortality and readmission risk following hospitalization or referral to the day clinic between ethnic minority groups (Surinamese, Turkish, Antilleans, Indonesians) and the ethnic Dutch population were investigated using Cox proportional hazard regression models with adjustment for age, sex, and comorbidities. Results: Age-sex-adjusted short-term and long-term risks of death following a first hospitalization with dementia were comparable between the ethnic minority groups and the ethnic Dutch. Age- and sex-adjusted risk of admission was higher only in Turkish compared with ethnic Dutch (HR 1.57, 95% CI,1.08–2.29). The difference between Turkish and the Dutch attenuated and was no longer statistically significant after further adjustment for comorbidities. There were no ethnic differences in short-term and long-term risk of death, and risk of readmission among day clinic patients. Conclusion: Compared with Dutch patients with a comparable comorbidity rate, ethnic minority patients with dementia did not have a worse prognosis. Given the poor prognosis of dementia, timely and targeted advance care planning is essential, particularly in ethnic minority groups who are mired by cultural barriers and where uptake of advance care planning is known to be low.
The Åstrand-Ryhming Test is not a Feasible Measure in Ambulatory Patients with Amyotrophic Lateral Sclerosis
Authors: van Groenestijn Annerieke C. , Verschuren Olaf , Schröder Carin D. , van den Berg Leonard H. , Visser-Meily Johanna M.A. 
Published: November 2016

Background: Ambulatory patients with Amyotrophic Lateral Sclerosis (ALS) show a decreased aerobic capacity which may hamper the ability to perform activities of daily living. A standardized measure, however, for assessing aerobic capacity in patients with ALS during the disease course, is lacking. Objective: To examine the feasibility of the Åstrand-Ryhming (ÅR) test protocol longitudinally in ambulatory patients with amyotrophic lateral sclerosis (ALS). Methods: Seven ambulatory male patients with spinal ALS onset were assessed at baseline and at 4, 7 and 10 months’ follow-up. Feasibility of the ÅR test protocol was analysed using percentage of: a) completed ÅR tests; b) achieved steady states; and c) predefined heart rates. Results: Test completion decreased from 7/7 at baseline to 10/21 at follow-up due to ALS-related symptoms as fatigue, muscle weakness and cramps. Steady states and predefined heart rates were achieved in 12/17 and 17/17 of the completed tests, respectively. Overall, the feasibility of the ÅR test protocol declines from 5/7 at baseline to 7/21 at follow-up. Conclusions: The results suggest that changes in aerobic capacity in ambulatory patients with ALS could not be successfully monitored due to a diminished feasibility of the ÅR test protocol.
European Cross-Sectional Survey of Current Care Practices for Duchenne Muscular Dystrophy Reveals Regional and Age-Dependent Differences
Authors: Vry Julia , Gramsch Kathrin , Rodger Sunil , Thompson Rachel , Steffensen Birgit F. , Rahbek Jes , Doerken Sam , Tassoni Adrian , Beytía María de los Angeles , Guergueltcheva Velina , Chamova Teodora , Tournev Ivailo , Kostera-Pruszczyk Anna , Kaminska Anna , Lusakowska Anna , Mrazova Lenka , Pavlovska Lenka , Strenkova Jana , Vondráček Petr , Garami Marta , Karcagi Veronika , Herczegfalvi Ágnes , Bushby Katherine , Lochmüller Hanns , Kirschner Janbernd 
Published: November 2016

Background: Publication of comprehensive clinical care guidelines for Duchenne muscular dystrophy (DMD) in 2010 was a milestone for DMD patient management. Our CARE-NMD survey investigates the neuromuscular, medical, and psychosocial care of DMD patients in Europe, and compares it to the guidelines. Methods: A cross-sectional survey of 1677 patients contacted via the TREAT-NMD patient registries was conducted using self-report questionnaires in seven European countries. Results: Survey respondents were 861 children and 201 adults. Data describe a European DMD population with mean age of 13.0 years (range 0.8–46.2) of whom 53% had lost ambulation (at 10.3 years of age, median). Corticosteroid medication raised the median age for ambulatory loss from 10.1 years in patients never medicated to 11.4 years in patients who received steroids ( p < 0.0001). The majority of patients reported receiving care in line with guidelines, although we identified significant differences between countries and important shortcomings in prevention and treatment. Summarised, 35% of patients aged≥ nine years received no corticosteroid medication, 24% of all patients received no regular physiotherapy, echocardiograms were not performed regularly in 22% of patients, pulmonary function was not regularly assessed in 71% of non-ambulatory patients. Patients with regular follow-up by neuromuscular specialists were more likely to receive care according to guidelines, were better satisfied, and experienced shorter unplanned hospitalization periods.
An update on larynx cancer
Authors: Steuer Conor E. , El‐Deiry Mark , Parks Jason R. , Higgins Kristin A. , Saba Nabil F. 
Published: November 2016

AbstractAnswer questions and earn CME/CNELaryngeal cancer remains one of the most common tumors of the respiratory tract. Fortunately, significant advancements have been made over the past decade in the treatment of laryngeal cancer. Although surgery has been the historical mainstay for localized disease and still is an integral part of treatment, nonsurgical options like radiation and systemic therapy have emerged as viable options. In addition, in the metastatic setting, novel agents are showing promise for this patient population. The care for patients with laryngeal cancer continues to evolve and truly requires a multidisciplinary team‐based approach. Unique morbidities, such as loss of natural voice, respiration, and airway protection during swallowing, are observed with this disease and require special consideration. CA Cancer J Clin 2017;67:31–50. © 2016 American Cancer Society.
Coléoptères Scarabaeoidea nouveaux de la faune Iranienne
Authors: Baraud Jacques 
Published: November 2016

Coléoptères Scarabaeoidea nouveaux de la Faune iranienne. Dans cet article, Scarabaeus crïstatus F. ssp. villiersi nov., est séparé de la forme nominative qui a été établie sur des exemplaires africains ; elle en diffère essentiellement par la forme du clypeus et des joues, par le tégument élytral luisant et par la forme des paramères.
Puis sont décrites 2 nouvelles espèces de Bolbocerini : Eubolbitus petrovitzi nov. sp. et Bolboceras davatchii nov. sp. Ces 2 espèces sont bien caractérisées et ne peuvent être confondues avec aucune autre ; à ce propos la division générique de la tribu des Bolbocerini est rappelée.
1. Sur les vols et populations de Myzus persicae en 1972
Authors: du Retail F. 
Published: November 2016

Trois observations sur le terrain sont présentées :
1 et 2. Ecologie des populations de Myzus persicae et de diverses coccinelles sur la betterave à sucre ou dans le boccage.
3. Signalisation d'un vol migrateur chez Hydrophilus piceus.
Contribution à l'étude hydrobiologique de trois cours d'eau du nord-ouest de la Tunisie. Présentation, physico-chimie et aperçu faunistique
Authors: Kraïem Mustapha 
Published: November 2016

Une comparaison morphodynamique, physico-chimique et faunistique de trois cours d'eau du nord-ouest de la Tunisie est réalisée.
Les secteurs concernés dans ces cours d'eau présentent des différences d'altitude, se traduisant par des différences dans la composition de la faune d'invertébrés. De plus, en période d'étiage, l'écoulement est complètement interrompu dans l'oued Béja, très réduit dans l'oued Ennour, mais plus régulier dans l'oued Ghezala. Dans les deux premiers, les populations de poissons sont alors fractionnées ; l'évaporation estivale produit une élévation considérable de la salinité et de la conductivité dans les oueds Béja et Ghezala. Par contre, toutes ces différences s'estompent en période de hautes eaux.
Introduction pratique à la systématique des organismes des eaux continentales françaises. - 9. Crustacés Branchiopodes (Anostracés, Notostracés, Conchostracés)
Authors: Nourisson Michel , Thiéry Alain 
Published: November 2016

Dans cet article, les auteurs proposent des clés simples présentées sous forme d'organigrammes illustrés permettant la détermination des genres et espèces d'Anostracés, de Notostracés et de Conchostracés répertoriés à ce jour en France.
Ces clés sont accompagnées des principales caractéristiques morphologiques, biologiques et écologiques du groupe. Pour chaque espèce sont fournies une iconographie détaillée et des remarques sur son écologie et sa répartition.
On trouvera dans la bibliographie d'une part les références d'ouvrages et articles fondamentaux concernant le groupe (morphologie, anatomie, biologie, taxonomie, écologie, répartition) et d'autre part un inventaire exhaustif des articles ayant trait plus particulièrement aux espèces de la faune de France.
La première guerre mondiale comme tournant pour l’institution monarchique en Grèce
Authors: Lemonidou Elli 
Published: November 2016

Le roi Constantin a joué un rôle majeur dans l’histoire de la Grèce au cours de la Première Guerre mondiale, soutenant d’une main ferme la neutralité du pays jusqu’au moment de sa destitution, en 1917. Homme de forte personnalité, Constantin s’opposa aux intentions et aux plans élaborés par le Premier ministre Elefthérios Vénizélos sur la question de l’entrée du pays dans la guerre aux côtés de l’Entente. Très tôt, le conflit entre les deux hommes, basé sur la question de la conduite à adopter face à la guerre devint pratiquement incontrôlable, créant ainsi le fondement du dénommé Schisme National, l’un des épisodes les plus traumatisants de l’histoire grecque moderne.	L’article examine les facteurs qui ont influencé conjointement la personnalité et les prises de décision de Constantin, et aussi ses actes durant la Première Guerre mondiale. La justification (et parfois la glorification) de la position de Constantin au cours de la Grande Guerre devint un solide point de référence pour tous les pro-royalistes dans les décennies qui suivirent sa mort. Il faut, pourtant, observer que, dans une perspective historique, la période 1914-1917 peut être considérée comme un tournant dans l’histoire de la royauté en Grèce, qui a ouvert la voie à une baisse progressive de l’attrait pour l’institution royale, qui, parvint cependant à survivre encore pour plusieurs décennies dans l’histoire turbulente du pays jusqu’à sa disparition définitive, par référendum, en 1974.