bluuebunny/crossref_metadata_2025_split huggingface dataset:
A TREM1 variant alters the accumulation of Alzheimer‐related amyloid pathology
Authors: Replogle Joseph M. , Chan Gail , White Charles C. , Raj Towfique , Winn Phoebe A. , Evans Denis A. , Sperling Reisa A. , Chibnik Lori B. , Bradshaw Elizabeth M. , Schneider Julie A. , Bennett David A. , De Jager Philip L. 
Published: December 2014

ObjectiveGenome‐wide association studies have linked variants in TREM2 (triggering receptor expressed on myeloid cells 2) and TREML2 with Alzheimer disease (AD) and AD endophenotypes. Here, we pursue a targeted analysis of the TREM locus in relation to cognitive decline and pathological features of AD.MethodsClinical, cognitive, and neuropathological phenotypes were collected in 3 prospective cohorts on aging (n = 3,421 subjects). Our primary analysis was an association with neuritic plaque pathology. To functionally characterize the associated variants, we used flow cytometry to measure TREM1 expression on monocytes.ResultsWe provide evidence that an intronic variant, rs6910730G, in TREM1, is associated with an increased burden of neuritic plaques (p = 3.7 × 10−4), diffuse plaques (p = 4.1 × 10−3), and Aβ density (p = 2.6 × 10−3) as well as an increased rate of cognitive decline (p = 5.3 × 10−3). A variant upstream of TREM2, rs7759295C, is independently associated with an increased tau tangle density (p = 4.9 × 10−4), an increased burden of neurofibrillary tangles (p = 9.1 × 10−3), and an increased rate of cognitive decline (p = 2.3 × 10−3). Finally, a cytometric analysis shows that the TREM1 rs6910730G allele is associated with decreased TREM1 expression on the surface of myeloid cells (p = 1.7 × 10−3).InterpretationWe provide evidence that 2 common variants within the TREM locus are associated with pathological features of AD and aging‐related cognitive decline. Our evidence suggests that these variants are likely to be independent of known AD variants and that they may work through an alteration of myeloid cell function. Ann Neurol 2015;77:469–477
Switch to natalizumab versus fingolimod in active relapsing–remitting multiple sclerosis
Authors: Kalincik Tomas , Horakova Dana , Spelman Tim , Jokubaitis Vilija , Trojano Maria , Lugaresi Alessandra , Izquierdo Guillermo , Rozsa Csilla , Grammond Pierre , Alroughani Raed , Duquette Pierre , Girard Marc , Pucci Eugenio , Lechner‐Scott Jeannette , Slee Mark , Fernandez‐Bolanos Ricardo , Grand'Maison Francois , Hupperts Raymond , Verheul Freek , Hodgkinson Suzanne , Oreja‐Guevara Celia , Spitaleri Daniele , Barnett Michael , Terzi Murat , Bergamaschi Roberto , McCombe Pamela , Sanchez‐Menoyo Jose , Simo Magdolna , Csepany Tunde , Rum Gabor , Boz Cavit , Havrdova Eva , Butzkueven Helmut ,   on behalf of the MSBase Study Group
Published: December 2014

ObjectiveIn patients suffering multiple sclerosis activity despite treatment with interferon β or glatiramer acetate, clinicians often switch therapy to either natalizumab or fingolimod. However, no studies have directly compared the outcomes of switching to either of these agents.MethodsUsing MSBase, a large international, observational, prospectively acquired cohort study, we identified patients with relapsing–remitting multiple sclerosis experiencing relapses or disability progression within the 6 months immediately preceding switch to either natalizumab or fingolimod. Quasi‐randomization with propensity score–based matching was used to select subpopulations with comparable baseline characteristics. Relapse and disability outcomes were compared in paired, pairwise‐censored analyses.ResultsOf the 792 included patients, 578 patients were matched (natalizumab, n = 407; fingolimod, n = 171). Mean on‐study follow‐up was 12 months. The annualized relapse rates decreased from 1.5 to 0.2 on natalizumab and from 1.3 to 0.4 on fingolimod, with 50% relative postswitch difference in relapse hazard (p = 0.002). A 2.8 times higher rate of sustained disability regression was observed after the switch to natalizumab in comparison to fingolimod (p < 0.001). No difference in the rate of sustained disability progression events was observed between the groups. The change in overall disability burden (quantified as area under the disability–time curve) differed between natalizumab and fingolimod (−0.12 vs 0.04 per year, respectively, p < 0.001).InterpretationThis study suggests that in active multiple sclerosis during treatment with injectable disease‐modifying therapies, switching to natalizumab is more effective than switching to fingolimod in reducing relapse rate and short‐term disability burden. Ann Neurol 2015;77:425–435
Magnetic resonance imaging pattern learning in temporal lobe epilepsy: Classification and prognostics
Authors: Bernhardt Boris C. , Hong Seok‐Jun , Bernasconi Andrea , Bernasconi Neda 
Published: December 2014

ObjectiveIn temporal lobe epilepsy (TLE), although hippocampal atrophy lateralizes the focus, the value of magnetic resonance imaging (MRI) to predict postsurgical outcome is rather modest. Prediction solely based on the hippocampus may be hampered by widespread mesiotemporal structural damage shown by advanced imaging. Increasingly complex and high‐dimensional representation of MRI metrics motivates a shift to machine learning to establish objective, data‐driven criteria for pathogenic processes and prognosis.MethodsWe applied clustering to 114 consecutive unilateral TLE patients using 1.5T MRI profiles derived from surface morphology of hippocampus, amygdala, and entorhinal cortex. To evaluate the diagnostic validity of the classification, we assessed its yield to predict outcome in 79 surgically treated patients. Reproducibility of outcome prediction was assessed in an independent cohort of 27 patients evaluated on 3.0T MRI.ResultsFour similarly sized classes partitioned our cohort; in all, alterations spanned over the 3 mesiotemporal structures. Compared to 46 controls, TLE‐I showed marked bilateral atrophy; in TLE‐II atrophy was ipsilateral; TLE‐III showed mild bilateral atrophy; whereas TLE‐IV showed hypertrophy. Classes differed with regard to histopathology and freedom from seizures. Classwise surface‐based classifiers accurately predicted outcome in 92 ± 1% of patients, outperforming conventional volumetry. Predictors of relapse were distributed bilaterally across structures. Prediction accuracy was similarly high in the independent cohort (96%), supporting generalizability.InterpretationWe provide a novel description of individual variability across the TLE spectrum. Class membership was associated with distinct patterns of damage and outcome predictors that did not spatially overlap, emphasizing the ability of machine learning to disentangle the differential contribution of morphology to patient phenotypes, ultimately refining the prognosis of epilepsy surgery. Ann Neurol 2015;77:436–446
Extraction protease expressed by Penicillium fellutanum from the Brazilian savanna using poly(ethylene glycol)/sodium polyacrylate/NaCl aqueous two‐phase system
Authors: Barros Kleber V. G. , Souza Paula M. , Cardoso Samuel L. , Borges Leonardo L. , Filho Edivaldo X. F. , Junior Adalberto P. , Magalhães Pérola O. 
Published: December 2014

AbstractThe partitioning of protease expressed by Penicillium fellutanum from the Brazilian savanna in a novel inexpensive and stable aqueous two‐phase system (ATPS) composed of poly(ethylene glycol) (PEG) and sodium polyacrylate (NaPA) was studied in this work using factorial design. The ATPS is formed by mixing both polymers with a salt (NaCl) and fermented broth of P. fellutanum. The effects of molar mass (2,000, 4,000, and 6,000 g⋅mol−1) and concentration (6, 8, and 10 wt%) of PEG and that of NaPA concentration (6, 8, and 10 wt%) on protease partitioning (K) at 25 °C were studied. A two‐level factorial design (23) was implemented. The effect of Na2SO4 concentration (5, 10, and 15 wt%) on the reextraction of the enzyme was also analyzed. The partition coefficient K ranged from 77.51 to 1.21, indicating the versatility of the method. The reextraction was achieved with the addition of 5% Na2SO4, allowing the partitioning of the protease to the upper phase, whereas total proteins were directed to the bottom phase. The results of partitioning using the PEG/NaPA/NaCl system and that of the subsequent reextraction with Na2SO4 suggest that this method can be used to purify proteases from fermented broth of P. fellutanum.
Review toward all RNA structures, concisely
Authors: Weeks Kevin M. 
Published: December 2014

ABSTRACTProfound insights regarding nucleic acid structure and function can be gleaned from very simple, direct, and chemistry‐based strategies. Our approach strives to incorporate the elegant physical insights that Don Crothers instilled in those who trained in his laboratory. Don emphasized the advantages of focusing on direct and concise experiments even when the final objective was to understand something complex—potentially including the large‐scale architectures of the genomes of RNA viruses and the transcriptomes of cells. Here, the author reviews the intellectual path, and a few detours, that led to the development of the SHAPE‐MaP and RING‐MaP technologies for interrogating RNA structure and function at large scales. The author also argues that greater attention to creating direct, less inferential experiments will convert “omics” investigations into lasting and definitive contributions to our understanding of biological function. © 2014 Wiley Periodicals, Inc. Biopolymers 103: 438–448, 2015.
Meeting report: SMART timing—principles of single molecule techniques course at the University of Michigan 2014
Authors: Bartke Rebecca M. , Cameron Elizabeth L. , Cristie‐David Ajitha S. , Custer Thomas C. , Denies Maxwell S. , Daher May , Dhakal Soma , Ghosh Soumi , Heinicke Laurie A. , Hoff J. Damon , Hou Qian , Kahlscheuer Matthew L. , Karslake Joshua , Krieger Adam G. , Li Jieming , Li Xiang , Lund Paul E. , Vo Nguyen N. , Park Jun , Pitchiaya Sethuramasundaram , Rai Victoria , Smith David J. , Suddala Krishna C. , Wang Jiarui , Widom Julia R. , Walter Nils G. 
Published: December 2014

ABSTRACTFour days after the announcement of the 2014 Nobel Prize in Chemistry for “the development of super‐resolved fluorescence microscopy” based on single molecule detection, the Single Molecule Analysis in Real‐Time (SMART) Center at the University of Michigan hosted a “Principles of Single Molecule Techniques 2014” course. Through a combination of plenary lectures and an Open House at the SMART Center, the course took a snapshot of a technology with an especially broad and rapidly expanding range of applications in the biomedical and materials sciences. Highlighting the continued rapid emergence of technical and scientific advances, the course underscored just how brightly the future of the single molecule field shines. © 2014 Wiley Periodicals, Inc. Biopolymers 103: 296–302, 2015.
Review fifteen years of search for strong nucleosomes
Authors: Trifonov Edward N. , Nibhani Reshma 
Published: December 2014

ABSTRACTDon Crothers, Mikael Kubista, Jon Widom, and their teams have been first to look for strong nucleosomes, in a bid to reveal the nucleosome positioning pattern(s) carried by the nucleosome DNA sequences. They were first to demonstrate that the nucleosome stability correlates with 10–11 base sequence periodicity, and that the strong nucleosomes localize preferentially in centromeres. This review describes these findings and their connection to recent discovery of the strong nucleosomes (SNs) with visibly periodic nucleosome DNA sequences. © 2014 Wiley Periodicals, Inc. Biopolymers 103: 432–437, 2015.
Simultaneous determination of ten flavonoids of crude and wine‐processed Radix Scutellariae aqueous extracts in rat plasma by UPLC‐ESI‐MS/MS and its application to a comparative pharmacokinetic study
Authors: Cui Xiao‐Bing , Qian Xiao‐Cui , Huang Ping , Zhang Yong‐Xin , Li Jun‐Song , Yang Guang‐Ming , Cai Bao‐Chang 
Published: December 2014

AbstractRadix Scutellariae (RS) is a herbal medicine with various pharmacological activities to treat inflammation, respiratory and gastrointestinal infections, etc. In this study, a rapid, sensitive and selective UPLC‐ESI‐MS/MS method was developed for simultaneous determination of 10 flavonoids – scutellarin, scutellarein, chrysin, wogonin, baicalein, apigenin, wogonoside, oroxylin A‐7‐O‐glucuronide, oroxylin A and baicalin – from RS aqueous extracts in rat plasma with propyl paraben as internal standard (IS). Chromatographic separation was achieved on a C18 column using gradient elution with the mobile phase consisting of methanol and water (containing 0.1% formic acid) at a flow rate of 0.2 mL/min. The detection was performed in multiple reaction monitoring mode using electrospray ionization in negative mode. The validated method showed good linearity over a wide concentration range (r >0.9935). The intra‐ and interday assay variabilities were <9.5% and <12.4% for all analytes, respectively. The extraction recovery ranged from 71.2 to 89.7% for each analyte and IS. This method was successfully applied to pharmacokinetic comparision after oral administration of crude and wine‐processed RS aqueous extracts. There were significant differences in some pharmacokinetic parameters of most analytes between crude and wine‐processed RS. This suggested that wine‐processing exerted effects absorption of most flavonoids. Copyright © 2014 John Wiley & Sons, Ltd.
Separation and identification of multiple constituents in Xiao Chai Hu Decoction (Sho‐saiko‐to) by bioactivity‐guided fractionation combined with LC‐ESI‐QTOFMS/MS
Authors: Wu Yingying , Peng Ying , Song Cui , Li Lingzhi , Ma Hui , Li Danqi , Wang Fang , Yang Jingyu , Song Shaojiang , Wu Chunfu 
Published: December 2014

AbstractXiao Chai Hu Decoction (XCHD), named Sho‐saiko‐to in Japanese, is a well‐known traditional Chinese medicine formula used in Asia. However, the characterization methods used in the past have lacked sensitivity and the nature of the active constituents of XCHD remains unclear. This study was carried out to establish the hyphenated method of bioactivity‐guided fractionation and liquid chromatography coupled with electrospray ionization quadrupole time‐of‐flight mass spectrometry (LC‐ESI‐QTOFMS/MS) in order to identify the major bioactive constituents of XCHD. D101 macroporous resin was used to separate and enrich the material base into four fractions, XCHD‐1, XCHD‐2, XCHD‐3 and XCHD‐4. Each fraction was then evaluated for its antidepressant effect using depression‐related parameters. An LC‐ESI‐QTOFMS/MS method in both positive and negative ion mode was also applied for separation and identification of the biological active fractions of XCHD. As a result, 79 compounds including polysaccharides, flavonoids, saikosaponins, ginsenosides, licoricesaponins and gingerols were detected, 69 of them were identified or tentatively characterized. Based on our preliminary characterization investigations, polysaccharides, gingerols and flavonoids in XCHD may contribute to the antidepressant effect of XCHD. In conclusion, the hyphenated method of bioactivity‐guided fractionation and LC‐ESI‐QTOFMS/MS was meaningful for the isolation and preliminary identification of the biological active components in complex matrices of traditional Chinese medicine. Copyright © 2014 John Wiley & Sons, Ltd.
Shotgun metabolomic profiles in maternal urine identify potential mass spectral markers of abnormal fetal biochemistry – dihydrouracil and progesterone in the metabolism of Down syndrome
Authors: Trivedi Drupad K. , Iles Ray K. 
Published: December 2014

AbstractIn Down syndrome (DS) in particular, the precise cellular mechanisms linking genotype to phenotype is not straightforward despite a clear mapping of the genetic cause. Metabolomic profiling might be more revealing in understanding molecular–cellular mechanisms of inborn errors of metabolism/syndromes than genomics alone and also result in new prenatal screening approaches. The urinary metabolome of 122 maternal urine from women with and without an aneuploid pregnancy (predominantly Down syndrome) were compared by both zwitterionic hydrophilic interaction chromatography (ZIC‐HILIC) and reversed‐phase liquid chromatography (RPLC) coupled to hybrid ion trap time of flight mass spectral analysis. ZIC‐HILIC mass spectrometry resolved 10‐fold more unique molecular ions than RPLC mass spectrometry, of which molecules corresponding to ions of m/z 114.07 and m/z 314.20 showed maternal urinary level changes that significantly coincided with the presence of a DS fetus. The ion of m/z 314.20 was identified as progesterone and m/z 114.07 as dihydrouracil. A metabolomics profiling‐based maternal urinary screening test modelled from this separation data would detect approximately 87 and 60.87% (using HILIC‐MS and RPLC‐MS, respectively) of all DS pregnancies between 9 and 23 weeks of gestation with no false positives. Copyright © 2014 John Wiley & Sons, Ltd.
Intracellular ESAT‐6: A new biomarker for Mycobacterium tuberculosis infection
Authors: Poulakis Nikolaos , Gritzapis Angelos D. , Ploussi Maria , Leventopoulos Michail , Papageorgiou Chrysovalantis V. , Anastasopoulos Andreas , Constantoulakis Pantelis , Karabela Simona , Vogiatzakis Evangelos , Tsilivakos Vassilis 
Published: December 2014

BackgroundEarly secreted antigenic target 6 (ESAT‐6) is a virulent factor of Mycobacterium tuberculosis (MTB). The identification of intracellular (i/c) ESAT‐6 in host cells would be a direct marker of MTB infection. We developed a method to detect i/cESAT‐6 by flow cytometry. The aim of this study is to investigate the expression of i/cESAT‐6 in the host cells of individuals with MTB infection.MethodsThe expression of i/cESAT‐6 was examined in the blood of 58 active TB patients, in 10 naïve to TB infection controls, in 17 patients who completed anti‐TB treatment, and in 56 close contacts with an index TB case. Additionally, it was examined in the sputum of 12 active TB patients.ResultsThe i/cESAT‐6 was positively detected in the blood of 52 out of 58 (90%) active TB patients. All naïve to TB infection controls were negative. Three out of 17 (18%) patients at the end of anti‐TB treatment were positive. Twenty‐six out of 56 (46%) close contacts tested positive. The i/cESAT‐6 was detected in all culture positive TB sputum specimens.ConclusionsThe i/cESAT‐6 is a promising biomarker of MTB infection that could be used in the evaluation of active TB patients and in the diagnosis of latent TB infection. Further studies are needed to validate its potential diagnostic role. © 2014 International Clinical Cytometry Society
Sensitivity of high‐risk HPVHybrid Capture II (hrHPV HC2) test using SurePathTM specimens in the prediction of cervical high‐grade squamous lesions
Authors: Zhou Fang , Pulinthanathu Rajiv , Elgert Paul , Cangiarella Joan , Simsir Aylin 
Published: December 2014

IntroductionHigh‐risk HPV (hrHPV) testing is now considered standard of care in the detection and management of cervical high‐grade squamous intraepithelial lesions (HSIL/CIN 2–3) and their precursors. Recently, there has been concern in the scientific literature and lay media about the lack of data regarding the false‐negative rate (FNR) of HPV testing on SurePathTM cytology specimens. This is a critical issue, since guidelines on the management of Pap test abnormalities rely heavily on HPV status. We undertook this study to determine whether HPV testing on SurePathTM specimens is less sensitive compared to reports in the literature for ThinPrep®.MethodsWe identified women with new diagnoses of CIN 2, CIN 3, and squamous cell carcinoma (SCC) on biopsy or excision in 2009–2013. For each patient, we recorded all SurePathTM cytology and hrHPV HC2 (high‐risk HPV Hybrid Capture 2) test results from within 5 years prior to histologic diagnosis. Using the histologic diagnosis as the gold standard, we calculated the sensitivities of cytology and hrHPV HC2 tests for the detection of CIN 2, 3, and SCC. Our findings are based only on women who underwent biopsy or excision after having an abnormal cytology and/or positive HPV result.ResultsIn our cohort, the sensitivity of testing in the 5 years prior to histologic diagnosis of CIN 2, 3, and SCC (combined as a single group) is 98.4% for SurePathTM cytology, 95.3% for hrHPV HC2, and 100% if both tests are used together. No conclusion can be drawn regarding testing for SCC alone, because there was only one case of SCC.ConclusionOur results show that the false‐negative rate of hrHPV HC2 testing on SurePathTM specimens for the detection of CIN 2 and CIN 3 is low and comparable to that of ThinPrep® specimens. Diagn. Cytopathol. 2015;43:381–387. © 2014 Wiley Periodicals, Inc.
Determination of beta‐agonists in swine hair by μFIA and chemiluminescence
Authors: Chen Xu , Luo Yong , Shi Bo , Gao Zhigang , Du Yuguang , Liu Xianming , Zhao Weijie , Lin Bingcheng 
Published: December 2014

β‐Agonists are a group of illegal feed additives. In this paper, it was found that the light emission produced by the oxidation of luminol by potassium ferricyanide was enhanced by the β‐agonists (ractopamine, salbutamol, and terbutaline). Based on chemiluminescence phenomenon, a novel, rapid, and sensitive microflow injection analysis system on a microfluidic glass chip was established for determination of the β‐agonists. The chip was fabricated from two glass plates (64 mm × 32 mm) with microchannels of 200 μm width and 100 μm depth. The detection limits were achieved at 2.0 × 10−8 mol/L of ractopamine, 1.0 × 10−8 mol/L of terbutaline and 5.0 × 10−7 mol/L of salbutamol. In this report, our method was applied for determination of the β‐agonists in swine hair from three different sources with satisfactory results.
Superadditive opercular activation to food flavor is mediated by enhanced temporal and limbic coupling
Authors: Seubert Janina , Ohla Kathrin , Yokomukai Yoshiko , Kellermann Thilo , Lundström Johan N. 
Published: December 2014

AbstractFood perception is characterized by a transition from initially separate sensations of the olfactory and gustatory properties of the object toward their combined sensory experience during consumption. The holistic flavor experience, which occurs as the smell and taste merge, extends beyond the mere addition of the two chemosensory modalities, being usually perceived as more object‐like, intense and rewarding. To explore the cortical mechanisms which give rise to olfactory–gustatory binding during natural food consumption, brain activation during consumption of a pleasant familiar beverage was contrasted with presentation of its taste and orthonasal smell alone. Convergent activation to all presentation modes was observed in executive and chemosensory association areas. Flavor, but not orthonasal smell or taste alone, stimulated the frontal operculum, supporting previous accounts of its central role in the formation of the flavor percept. A functional dissociation was observed in the insula: the anterior portion was characterized by sensory convergence, while mid‐dorsal sections activated exclusively to the combined flavor stimulus. psycho‐physiological interaction analyses demonstrated increased neural coupling between the frontal operculum and the anterior insula during flavor presentation. Connectivity was also increased with the lateral entorhinal cortex, a relay to memory networks and central node for contextual modulation of olfactory processing. These findings suggest a central role of the insular cortex in the transition from mere detection of chemosensory convergence to a superadditive flavor representation. The increased connections between the frontal operculum and medial temporal memory structures during combined olfactory–gustatory stimulation point to a potential mechanism underlying the acquisition and modification of flavor preferences. Hum Brain Mapp 36:1662–1676, 2015. © 2014 Wiley Periodicals, Inc.