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Machine Learning to Detect Alzheimer’s Disease from Circulating Non-coding RNAs

Genomics, Proteomics & Bioinformatics 2019年第4期17卷 430-440页

作者： Nicole Ludwig Tobias Fehlmann Fabian Kern Manfred Gogol Walter Maetzler Stephanie Deutscher Simone Gurlit claudia schulte Anna-Katharina von Thaler Christian Deuschle Florian Metzger Daniela Berg Ulrike Suenkel Verena Keller Christina Backes Hans-Peter Lenhof Eckart Meese Andreas Keller Department of Human Genetics Saarland University66421 Homburg/SaarGermany Chair for Clinical Bioinformatics Saarland University66123 Saarbru¨ckenGermany Institut fur Gerontologie Universitat Heidelberg69047 HeidelbergGermany Department of Neurology Christian-Albrechts-University of Kiel24118 KielGermany Center for Neurology and Hertie Institute for Clinical Brain Research Department of NeurodegenerationUniversity of Tuebingen72074 TuebingenGermany German Center for Neurodegenerative Diseases(DZNE) 72076 TuebingenGermany Department of Anesthesiology and Intensive Care St.Franziskus Hospital Muenster48145 MuensterGermany Department of Psychiatry and Psychotherapy University Hospital Tuebingen72016 TuebingenGermany Department of Medicine II Saarland University Medical Center66421 Homburg/SaarGermany Center for Bioinformatics Saarland Informatics Campus66123 SaarbruckenGermany

Blood-borne small non-coding(snc RNAs)are among the prominent candidates for blood-based diagnostic ***,high-throughput approaches are applied to discover biomarker *** have to be validated in larger cohorts and evaluated by adequate statistical learning ***,we published high-throughput sequencing based microRNA(miRNA)signatures in Alzheimer’s disease(AD)patients in the United States(US)and ***,we determined abundance levels of 21 known circulating miRNAs in 465 individuals encompassing AD patients and controls by *** computed models to assess the relation between miRNA expression and phenotypes,gender,age,or disease severity(Mini-Mental State Examination;MMSE).Of the 21 miRNAs,expression levels of 20 miRNAs were consistently de-regulated in the US and German cohorts.18 miRNAs were significantly correlated with neurodegeneration(Benjamini-Hochberg adjusted P<0.05)with highest significance for miR-532-5 p(BenjaminiHochberg adjusted P=4.8×10^-30).Machine learning models reached an area under the curve(AUC)value of 87.6%in differentiating AD patients from ***,ten miRNAs were significantly correlated with MMSE,in particular miR-26a/26b-5p(adjusted P=0.0002).Interestingly,the miRNAs with lower abundance in AD were enriched in monocytes and T-helper cells,while those up-regulated in AD were enriched in serum,exosomes,cytotoxic t-cells,and *** study represents the next important step in translational research for a miRNA-based AD test.

关键词： miRNAs Neurodegeneration Alzheimer’s disease Biomarker Non-coding RNAs Gene regulation

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No association between Parkinson disease and autoantibodies against NMDA-type glutamate receptors

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Translational Neurodegeneration 2019年第1期8卷 127-133页

作者： Franziska Hopfner Stefanie HMüller Dagmar Steppat Joanna Miller Nele Schmidt Klaus-Peter Wandinger Frank Leypoldt Daniela Berg Andre Franke Wolfgang Lieb Lukas Tittmann Monika Balzer-Geldsetzer Simon Baudrexel Richard Dodel Ruediger Hilker-Roggendorf Elke Kalbe Jan Kassubek Thomas Klockgether Inga Liepelt-Scarfone Brit Mollenhauer Petra Neuser Kathrin Reetz Oliver Riedel claudia schulte Jörg BSchulz Annika Spottke Alexander Storch claudia Trenkwalder Hans-Ulrich Wittchen Karsten Witt Ullrich Wüllner Günther Deuschl Gregor Kuhlenbäumer Department of Neurology University Hospital Schleswig HolsteinArnold-Heller Str.324105 KielGermany Center of Blood Transfusion University Hospital Schleswig HolsteinKiel&LübeckGermany Department of Clinical Chemistry University Hospital Schleswig-HolsteinKielGermany Institute of Clinical Molecular Biology University Hospital Schleswig-HolsteinKielGermany Institute of Epidemiology University Hospital Schleswig-HolsteinKielGermany Chair of Geriatric Medicine University Hospital EssenEssenGermany Department of Neurology Philipps-University MarburgMarburgGermany Department of Neurology Goethe UniversityFrankfurt/MainGermany Brain Imaging Center Goethe UniversityFrankfurt/MainGermany Department of Medical Psychology|Neuropsychology and Gender Studies&Center for Neuropsychological Diagnostics and Intervention(CeNDI) University Hospital CologneCologneGermany Psychological Gerontology Institute of GerontologyUniversity of VechtaVechtaGermany Department of Neurology University of UlmUlmGermany Department of Neurology University of Bonnand German Center for Neurodegenerative Diseases(DZNE)BonnGermany Center for Neurology Hertie Institute for Clinical Brain ResearchDepartment of Neurodegenerative DiseasesUniversity of TübingenTübingenGermany DZNE German Center for Neurodegenerative DiseasesTübingenGermany Paracelsus-Elena-Klinik KasselGermany Institute of Neuropathology and Department of Neurosurgery University Medical Center GöttingenGöttingenGermany Coordinating Centre for Clinical Trials Philipps-UniversityMarburgGermany Department of Neurology RWTH Aachen UniversityAachenGermany JARA-BRAIN Institute of Molecular Neuroscience and Neuroimaging Forschungszentrum Jülich GmbH and RWTH Aachen UniversityAachenGermany Leibniz Institute for Prevention Research and Epidemiology-BIPS Achterstrasse 3028359 BremenGermany Department of Neurology Technische Universität Dresden01307 DresdenGermany German Center for Neurodegenerative Diseases(DZNE) Research Site Rostock18147 RostockGerma

Background:IgG-class autoantibodies to N-Methyl-D-Aspartate(NMDA)-type glutamate receptors define a novel entity of autoimmune *** examining the prevalence of NMDA IgA/IgM antibodies in patients with Parkinson disease with/without dementia produced conflicting *** measured NMDA antibodies in a large,well phenotyped sample of Parkinson patients without and with cognitive impairment(n=296)and controls(n=295)free of neuropsychiatric *** phenotyping and large numbers allowed statistically meaningful correlation of antibody status with diagnostic subgroups as well as quantitative indicators of disease severity and cognitive ***:NMDA antibodies were analysed in the serum of patients and controls using well established validated *** used anti-NMDA antibody positivity as the main independent variable and correlated it with disease status and phenotypic ***:The frequency of NMDA IgA/IgM antibodies was lower in Parkinson patients(13%)than in controls(22%)and higher than in previous studies in both *** IgA/IgM antibodies were neither significantly associated with diagnostic subclasses of Parkinson disease according to cognitive impairment,nor with quantitative indicators of disease severity and cognitive impairment.A positive NMDA antibody status was positively correlated with age in controls but not in Parkinson ***:It is unlikely albeit not impossible that NMDA antibodies play a significant role in the pathogenesis or progression of Parkinson disease *** Parkinson disease with dementia,while NMDA IgG antibodies define a separate disease of its own.

关键词： NMDA antibody NMDA IgA/IgM antibodies Parkinson disease Cognitive impairment

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Software improvement for evaluation of laryngopharyngeal pH testing(Restech)——a comparison between Data View 3 and 4

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World Journal of Gastrointestinal Surgery 2020年第5期12卷 236-246页

作者： Dolores Thea Müller Elena schulte Benjamin Babic Laura Knepper claudia Fuchs Wolfgang Schroder Christiane J Bruns Jessica M Leers Hans Friedrich Fuchs Department of General VisceralCancer and Transplant SurgeryUniversity of CologneKoln 50937Germany

BACKGROUND When gastroesophageal reflux contents reach above the upper esophageal sphincter,patients may,in addition to typical reflux symptoms,present with atypical,extraesophageal symptoms related to laryngopharyngeal reflux(LPR).Surgical treatment of LPR has shown to lead to 70%symptom improvement,however no gold standard for the diagnosis of LPR *** 2007,the Restech Dx-pH was released as a valid method to measure acid exposure above the upper esophageal ***,a new software update was introduced for analysis of measured pH data and calculation of composite *** effect of the changes applied to the new software version have not yet been *** To compare results generated by Data View 3 to the most recently released Data View *** All patients with gastroesophageal reflux disease symptoms were seen in a specialized surgical outpatient clinic for gastrointestinal function *** chart review was performed of all patients presenting with suspected gastroesophageal reflux disease and extraesophageal reflux symptoms,who underwent laryngopharyngeal pH monitoring using the Restech Dx-pH system(Respiratory Technology Corp.,Houston,TX,United States)and simultaneous esophageal pH *** View 3 and Data View 4 were used to evaluate Restech studies *** entries such as mealtimes,supine and upright periods,and symptoms were entered manually to ensure accuracy and precise conversion of data between both software *** t test was performed for statistical analysis of *** A total of 174 patients(63.8%female)met inclusion criteria,all suffering from extraesophageal reflux symptoms as well as typical gastroesophageal reflux disease *** RYAN score upright was 48.77 in Data View 3 compared to 22.17 in Data View 4,showing a significant difference(~aP=0.0001).Similar results were shown for supine period(mean RYAN Score Data View 35.29 vs 1.42 in Data View 4,~cP=0.0001).For upright pe

关键词： Gastroesophageal reflux disease Laryngopharyngeal reflux disease Esophageal pH testing Oropharyngeal pH testing Restech Dx pH DeMeester score RYAN Score

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Acidification of the Skin and Maintenance of the Physiological Skin pH Value by Buffered Skin Care Products Formulated around pH 4

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Journal of Cosmetics, Dermatological Sciences and Applications 2021年第1期11卷 44-57页

作者： Anke schulte to Brinke Antje Mehlich claudia Doberenz Ciska Janssens-Böcker Department of Clinical Affairs MedSkin Solutions Dr. Suwelack AG Billerbeck Germany Department of Innovation and Development MedSkin Solutions Dr. Suwelack AG Billerbeck Germany

Each biological system possesses a widely unrecognized buffer system to maintain acid-base balance to a specific pH. The skin pH is crucial for physiological skin function. In aged or diseased skin, pH increase is observed and may negatively affect skin health. Skin care products with a pH that is slightly more acidic than the average normal skin pH and have an adequate buffering capacity, are considered beneficial for the skin. However, the buffer capacity of these products also plays an important role. In the present study, a possible normalization or acidification of skin surface pH and influence on skin hydration and skin barrier function was assessed via application of buffered skin care products that are formulated with pH ≤ 4.5. 48 subjects aged above 50 were treated with three different skin care products (Vitamin C Spheres, Collagen Spray, and Collagen Mask) and skin surface pH, skin hydration and barrier integrity were assessed before treatment start and after 4 weeks. The results show that after 4-week treatment with Vitamin C, the skin pH is acidified. Treatment with Collagen Spray and Collagen Mask showed maintenance of a physiological skin pH. Subgroup analysis of subjects that had a higher than average skin pH at study start demonstrated that all three tested skin care products were able to acidify the skin surface. In addition, skin hydration was also increased for two of the three tested products, whereas skin barrier is not significantly changed. This demonstrates that buffered skin care products formulated to a pH ≤ 4.5 are able to acidify and maintain physiological skin pH and may contribute to a physiological skin function.

关键词： Skin pH Buffer Capacity Skin Care Skin Aging Acidification

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Partial external biliary diversion in bile salt export pump deficiency: Association between outcome and mutation

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World Journal of Gastroenterology 2017年第29期23卷 5295-5303页

作者： Philipp Ellinger Jan Stindt Carola Droge Katharina Sattler claudia Stross Stefanie Kluge Diran Herebian Sander HJ Smits Martin Burdelski Sebastian Schulz-Jürgensen Antje Ballauff Jan schulte am Esch Ertan Mayatepek Dieter Haussinger Ralf Kubitz Lutz Schmitt In-stitute of Biochemistry Hein-rich-Hein-e-Un-iversity Düsseldorf Medical Faculty Departmen-t of Gastroen-terology Hepatology an-d In-fectious Diseases Hein-rich-Hein-e-Un-iversity Düsseldorf Departmen-t of Gen-eral Pediatrics Neon-atology an-d Pediatric Cardiology Medical Faculty Hein-rich-Hein-e-Un-iversity Düsseldorf Departmen-t of Paediatrics Un-iversity Hospital Schleswig Holstein- Departmen-t of Paediatrics Helios Clin-ic Departmen-t of Gen-eral Surgery Hein-rich-Hein-e-Un-iversity

AIM To investigate the relation of two different mutations to the outcome of partial external biliary diversion(PEBD)in severe bile salt export pump(BSEP) *** Mutations in the gene encoding BSEP leading to severe BSEP deficiency in two unrelated patients were identified by genomic sequencing. Native liver biopsies and transiently transfected human embryonic kidney(HEK) 293 cells expressing either wild-type or mutated BSEP were subjected to immunofluorescence analysis to assess BSEP transporter localization. Bile acid profiles of patient and control bile samples were generated by ultra-performance liquid chromatographytandem mass spectrometry. Wild-type and mutant BSEP transport of [~3H]-labeled taurocholate(TC) and taurochenodeoxycholate(TCDC) was assessed by vesicular transport *** A girl(at 2 mo) presented with pruritus, jaundice and elevated serum bile salts(BS). PEBD stabilized liver function and prevented liver transplantation. She was heterozygous for the BSEP deletion p.T919 del and the nonsense mutation p.R1235 X. At the age of 17 years relative amounts of conjugated BS in her bile were normal, while total BS were less than 3% as compared to controls. An unrelated boy(age 1.5 years) presenting with severe pruritus and elevated serum BS was heterozygous for the same nonsense and another missense mutation, p.G1032 R. PEBD failed to alleviate pruritus, eventually necessitating liver transplantation. BS concentration in bile was about 5% of controls. BS were mainly unconjugated with an unusual low amount of chenodeoxycholate derivatives(< 5%). The patients' native liver biopsies showed canalicular BSEP expression. Both BSEP p.T919 del and p.G1032 R were localized in the plasma membrane in HEK293 cells. In vitro transport assays showed drastic reduction of transport by both mutations. Using purified recombinant BSEP as quantifiable reference, per-molecule transport rates for TC and TCDC were determined to be 3 and 2 BS molecules per wild

关键词：家庭 intrahepatic cholestasis 类型 2 部分外部胆汁的转向胆汁盐出口泵 ATP 有约束力的盒子 transporter Intrahepatic cholestasis

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Acidification of the Skin and Maintenance of the Physiological Skin pH Value by Buffered Skin Care Products Formulated around pH 4

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Journal of Cosmetics, Dermatological Sciences and Applications 2021年第1期

作者： Anke schulte to Brinke Antje Mehlich claudia Doberenz Ciska Janssens-Böcker

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