bluuebunny/crossref_metadata_2025_split huggingface dataset:
De novo UNC13B mutation identified in a bipolar disorder patient increases a rare exon‐skipping variant
Authors: Nakamura Takumi , Jimbo Kotori , Nakajima Kazuo , Tsuboi Takashi , Kato Tadafumi 
Published: August 2018

AbstractAimWe previously performed the first trio‐based exome study for bipolar disorder and identified 71 de novo mutations. Among these mutations, the only mutation located at the splice donor site was in UNC13B. We focused on and analyzed the functions of the mutation.MethodsIn order to analyze the functional alterations, due to the mutation, we performed a minigene splicing assay.Key resultsWe found that the mutation caused the loss of a wild‐type splicing variant, which was consistent with the computational splice prediction, and that an exon‐skipping variant increased significantly. The exon‐skipping variant also existed in the wild‐type minigene, although it was rare. Hence, we validated the expression of the exon‐skipping variant using total RNAs derived from the human cerebral cortex. We showed the possibility that the exon‐skipping variant was rare, but expressed even in those that do not carry the mutation.ConclusionsBased on our results, we suggest that an abnormal splicing pattern of UNC13B occurred in the patient, which could be related to the pathophysiology of bipolar disorder.
A case of nonvenereal treponematosis in a pre‐Hispanic adult from north‐eastern Argentina
Authors: Ramos van Raap María Agustina , Scabuzzo Clara 
Published: August 2018

AbstractThis article presents a case of treponemic disease in a skeleton of a female adult found at Los Tres Cerros 1 archaeological site (Upper Delta of Paraná River, Entre Ríos, Argentina). This site was occupied by hunter–gatherer–fisher groups that also practised horticulture during the Late Holocene (ca. 1227–560 years BP). A macroscopic description of bone lesions is complemented with data from X‐rays and CT scans. Different types of lesions were observed in the left ulna, femora, right patella, tibiae, and fibulae. In addition, two remodelled depressions surrounded by bony thickening and porosities were found in the frontal bone. Some lesions registered in the skull were associated with caries sicca. In the differential diagnosis, chronic leg ulcers, Paget's disease, tuberculosis, leprosy, osteomyelitis, and treponematosis were considered. The analyses indicate that most of the injuries may be compatible with nonvenereal forms of treponematosis. Few cases of treponemic disease were recorded in Argentina's bioarchaeological collections of pre‐Hispanic populations. Specifically, in the north‐eastern region, two skeletons with treponematosis have so far been reported. The present study provides new evidence of treponematosis in the Delta of the Paraná River. Therefore, this case adds to the scant evidence of pre‐Hispanic treponematosis that exists for these latitudes.
The Western (Buonfornello) necropolis (7th to 5th BC) of the Greek colony of Himera (Sicily, Italy): Site‐specific discriminant functions for sex determination in the common burials resulting from the battle of Himera (ca. 480 BC)
Authors: Lonoce Norma , Palma Monica , Viva Serena , Valentino Matteo , Vassallo Stefano , Fabbri Pier Francesco 
Published: August 2018

AbstractThe Western (Buonfornello) necropolis of Himera, dating from the 7th to 5th century BC, has yielded 10,096 burials, among which are six common burials (n = 2–22). On the basis of the archaeological and historical evidence, these are presumed to be the result of the Battle of Himera, fought in approximately 480 BC, or some other warfare episode taking place in the same period, and it is hypothesised that all the individuals are male. A reliable morphological sex determination is impossible in most cases due to the bad state of preservation of the pelves. The present paper aims to establish whether sex dimorphism in diaphyseal dimensions allows for the calculation of site‐specific discriminant functions (DFs) that are useful for sex determination and to verify the archaeological hypothesis that all individuals in the six common burials are male. DF computation was conducted for sex determination based on the diaphyseal dimensions recorded for a sample of 89 pelvis sexed individuals (57 males and 32 females). The DFs were selected by taking into account the large number of m/f samples (n > 30) and the accuracy (>90%).DF was tested on a sample of male/female Himeran pelvis sexed individuals not used for computing DFs (n = 17, 11 males and 6 females) and 27 skeletons from common burials. In the first case, pelvis and DF sex determination are concordant in 16 cases (94.1%). In the second case, three out of 27 individuals were discarded as DFs produced conflicting sex determinations. The remaining 24 individuals were sexed as males by means of DFs in 95.8% of cases. The archaeological hypothesis that all individuals in these common burials are male cannot be rejected as site‐specific DFs diagnose the male sex in a percentage that is higher than their accuracy in a sample of pelvis sexed individuals.
Depressive symptoms and actigraphy‐measured circadian disruption predict head and neck cancer survival
Authors: Cash Elizabeth , Duck C. Riley , Brinkman Courtney , Rebholz Whitney , Albert Christy , Worthen Mary , Jusufbegovic Mia , Wilson Liz , Bumpous Jeffrey M. 
Published: August 2018

AbstractObjectiveDepressive symptoms have demonstrated prognostic significance among head and neck cancer patients. Depression is associated with circadian disruption, which is prognostic in multiple other cancer types. We hypothesized that depressive symptoms would be associated with circadian disruption in head and neck cancer, that each would be related to poorer 2‐year overall survival, and that relationships would be mediated by tumor response to treatment.MethodsPatients (N = 55) reported on cognitive/affective and somatic depressive symptoms (PHQ‐9) and wore an actigraph for 6 days to continuously record rest and activity cycles prior to chemoradiation. Records review documented treatment response and 2‐year survival. Spearman correlations tested depressive symptoms and circadian disruption relationships. Cox proportional hazard models tested the predictive capability of depressive symptoms and circadian disruption, separately, on survival.ResultsDepressive symptoms were significantly associated with circadian disruption, and both were significantly associated with shorter survival (somatic: hazard ratio [HR] = 1.325, 95% confidence interval [CI] = 1.089‐1.611, P = .005; rest/activity rhythm: HR = 0.073, 95% CI = 0.009‐0.563, P = .012; nighttime restfulness: HR = 0.910, 95% CI = 0.848‐0.977, P = .009). Tumor response to treatment appeared to partly mediate the nighttime restfulness‐survival relationship.ConclusionsThis study replicates and extends prior work with new evidence linking a subjective measure of depression and an objective measure of circadian disruption—2 known prognostic indicators—to shortened overall survival among head and neck cancer patients. Continued examination should elucidate mechanisms by which depressive symptomatology and circadian disruption translate to head and neck cancer progression and mortality.
Liquorice (Glycyrrhiza glabra): A phytochemical and pharmacological review
Authors: Pastorino Giulia , Cornara Laura , Soares Sónia , Rodrigues Francisca , Oliveira M. Beatriz P.P. 
Published: August 2018

In the last years, consumers are paying much more attention to natural medicines and principles, mainly due to the general sense that natural compounds are safe. On the other hand, there is a growing demand by industry for plants used in traditional medicine that could be incorporated in foods, nutraceuticals, cosmetics, or even pharmaceuticals. Glycyrrhiza glabra Linn. belongs to the Fabaceae family and has been recognized since ancient times for its ethnopharmacological values. This plant contains different phytocompounds, such as glycyrrhizin, 18β‐glycyrrhetinic acid, glabrin A and B, and isoflavones, that have demonstrated various pharmacological activities. Pharmacological experiments have demonstrated that different extracts and pure compounds from this species exhibit a broad range of biological properties, including antibacterial, anti‐inflammatory, antiviral, antioxidant, and antidiabetic activities. A few toxicological studies have reported some concerns. This review addresses all those issues and focuses on the pharmacological activities reported for G. glabra. Therefore, an updated, critical, and extensive overview on the current knowledge of G. glabra composition and biological activities is provided here in order to explore its therapeutic potential and future challenges to be utilized for the formulation of new products that will contribute to human well‐being.
Simultaneous quantification of atropine and scopolamine in infusions of herbal tea and Solanaceae plant material by matrix‐assisted laser desorption/ionization time‐of‐flight (tandem) mass spectrometry
Authors: John Harald , Rychlik Michael , Thiermann Horst , Schmidt Christian 
Published: August 2018

RationaleAtropine (Atr) and scopolamine (Scp) are toxic secondary plant metabolites of species within the Solanaceae genus that can accidentally or intentionally reach the food store chain by inaccurate harvesting of any plant material, e.g. for herbal tea infusions. Ingestion may cause severe anticholinergic poisoning thus requiring risk‐oriented determination in food and beverages. The suitability of matrix‐assisted laser desorption/ionization time‐of‐flight (tandem) mass spectrometry, MALDI‐TOF MS(/MS), should be characterized for simultaneous analysis.MethodsWe herein present the first MALDI‐TOF MS(/MS) procedure for quantitative determination of both alkaloids in herbal tea infusions and Solanaceae plant material. A standard additions procedure using triply deuterated Atr as internal standard was developed and validated.ResultsTropane alkaloids were detected without interferences and the standard additions procedure allowed reliable quantification. Intraday and interday precision were less than 17% and corresponding accuracies were between 77% and 112%. Limits of detection in the spotting solution were found at 5 ng/mL (Atr) and 0.5 ng/mL (Scp). The assay was applied to diverse tea infusions as well as to berries and leaves of deadly nightshade and angel's trumpet.ConclusionsThe usefulness of MALDI‐TOF MS(/MS) for investigations of plant‐derived samples to prove contaminations by small basic compounds was demonstrated. The elaborate procedure is reliable but quite laborious to obtain quantitative results, but MALDI‐TOF MS(/MS) was also shown to be a valuable tool for rapid qualitative screening for Atr and Scp in plant extracts.
Virtual reality simulation of robotic transsphenoidal brain tumor resection: Evaluating dynamic motion scaling in a master‐slave system
Authors: Heredia‐Pérez Saúl A. , Harada Kanako , Padilla‐Castañeda Miguel A. , Marques‐Marinho Murilo , Márquez‐Flores Jorge A. , Mitsuishi Mamoru 
Published: August 2018

AbstractBackgroundIntegrating simulators with robotic surgical procedures could assist in designing and testing of novel robotic control algorithms and further enhance patient‐specific pre‐operative planning and training for robotic surgeries.MethodsA virtual reality simulator, developed to perform the transsphenoidal resection of pituitary gland tumours, tested the usability of robotic interfaces and control algorithms. It used position‐based dynamics to allow soft‐tissue deformation and resection with haptic feedback; dynamic motion scaling control was also incorporated into the simulator.ResultsNeurosurgeons and residents performed the surgery under constant and dynamic motion scaling conditions (CMS vs DMS). DMS increased dexterity and reduced the risk of damage to healthy brain tissue. Post‐experimental questionnaires indicated that the system was well‐evaluated by experts.ConclusionThe simulator was intuitively and realistically operated. It increased the safety and accuracy of the procedure without affecting intervention time. Future research can investigate incorporating this simulation into a real micro‐surgical robotic system.
Electrochemical Activation of TTF‐Based Halogen Bond Donors: A Powerful, Selective and Sensitive Analytical Tool for Probing a Weak Interaction in Complex Media
Authors: Oliveira Raquel , Groni Sihem , Vacher Antoine , Barrière Frédéric , Lorcy Dominique , Fourmigué Marc , Maisonhaute Emmanuel , Schöllhorn Bernd , Fave Claire 
Published: August 2018

AbstractHerein we demonstrate the electrochemical activation and detection of intermolecular halogen bonding (XB) in solution by generating the cation radical of iodo‐trimethyltetrathiafulvalene (I‐Me3TTF•+) in the presence of various Lewis‐basic anions. This work is leading to the endorsement and generalization of the concept of electrostimulating XB for molecular recognition by adjusting the properties of the XB donor via the electrochemical reversible generation of charged species. The formation of the interaction between I–Me3TTF•+ and Lewis bases has been investigated by cyclic voltammetry allowing to quantify the strength of the interaction (KOx=100 to 400 M−1 and ΔG=−12 to −15 kJ mol−1). Moreover spectroelectrochemical measurements along with TD‐DFT calculations have confirmed XB formation upon generation of the radical cation. The present work opens broad perspectives for the development of redox switchable XB donors in the field of molecular recognition in chemical and biological systems where non‐covalent interactions are usually key governing parameters.
Generation of High‐Order All‐Aqueous Emulsion Drops by Osmosis‐Driven Phase Separation
Authors: Chao Youchuang , Mak Sze Yi , Rahman Shakurur , Zhu Shipei , Shum Ho Cheung 
Published: August 2018

AbstractDroplets containing ternary mixtures can spontaneously phase‐separate into high‐order structures upon a change in composition, which provides an alternative strategy to form multiphase droplets. However, existing strategies always involve nonaqueous solvents that limit the potential applications of the resulting multiple droplets, such as encapsulation of biomolecules. Here, a robust approach to achieve high‐order emulsion drops with an all‐aqueous nature from two aqueous phases by osmosis‐induced phase separation on a microfluidic platform is presented. This technique is enabled by the existence of an interface of the two aqueous phases and phase separation caused by an osmolality difference between the two phases. The complexity of emulsion drops induced by phase separation could be controlled by varying the initial concentration of solutes and is systematically illustrated in a state diagram. In particular, this technique is utilized to successfully achieve high‐order all‐aqueous droplets in a different aqueous two‐phase system. The proposed method is simple since it only requires two initial aqueous solutions for generating multilayered, organic‐solvent‐free all‐aqueous emulsion drops, and thus these multiphase emulsion drops can be further tailored to serve as highly biocompatible material templates.
A model‐based solution for process modeling in practice environments: PLM4BS
Authors: García‐García Julián Alberto , García‐Borgoñón Laura , Escalona María José , Mejías Manuel 
Published: August 2018

AbstractToday's world economic situation is ruled by issues such as reducing cost, improving quality, maximizing profit, and improving and optimizing processes at organizations. In this context, business process management can be an essential strategy, but it is not usually consolidated at software organizations because software process properties involve a complex business process management application on software lifecycle. Consequently, software organizations often focus on Software Process Modeling (SPM), and each involved role performs process execution and orchestration independently and manually. This fact makes software processes maintenance, monitoring, and measurement become difficult tasks. This paper proposes a model‐based approach for SPM taking into account concepts related to process execution, orchestration, and monitoring. It is framed into a model‐driven engineering‐based and tool‐based framework: Process Lifecycle Management for Business Software (PLM4BS). We present a SPM metamodel and its concrete syntax (through Unified Modeling Language profiles) that lays the foundation for extending PLM4BS. Its underlying metamodel allows managing processes automatically. Furthermore, PLM4BS improves current state‐of‐the‐art proposals in 6 dimensions: expressiveness, understandability, granularity, measurability, orchestrability, and business variables and rules. Also, PLM4BS has been evaluated in a multiple‐case study, in which the 6 mentioned dimensions were already validated.
FAHP approach for autonomic resource provisioning of multitier applications in cloud computing environments
Authors: Khorsand Reihaneh , Ghobaei‐Arani Mostafa , Ramezanpour Mohammadreza 
Published: August 2018

SummaryRecent advancements in web‐based application, especially in cloud computing environment, allows cloud service providers to deploy and provide web‐based services in the form of multitier applications. One of the most suitable infrastructure for the running of multitier applications is a cloud computing infrastructure. Since the arrival rate of users to the multitier applications varies over the time, deciding about the right amount of resources required to handle the each tier of multitier applications is not trivial, and it depends on the current workload of its each tier. Therefore, it is necessary to automatically provision resources to deal with fluctuating demands of the multitier applications. In this paper, we propose a hybrid resource provisioning approach for multitier applications based on a combination of the concept of the autonomic computing and the fuzzy analytical hierarchy process approach. Moreover, we present a framework based on MAPE‐k control loop for autonomous resource provisioning of multitier applications in cloud computing environments. The effectiveness of the proposed approach under real and synthetic workloads was evaluated. The experimental results indicate that the proposed solution outperforms in terms of allocated virtual machines, response time, and cost compared with the other approaches.
Glycogen synthase kinase‐3 and alternative splicing
Authors: Liu Xiaolei , Klein Peter S. 
Published: August 2018

Glycogen synthase kinase‐3 (GSK‐3) is a highly conserved negative regulator of receptor tyrosine kinase, cytokine, and Wnt signaling pathways. Stimulation of these pathways inhibits GSK‐3 to modulate diverse downstream effectors that include transcription factors, nutrient sensors, glycogen synthesis, mitochondrial function, circadian rhythm, and cell fate. GSK‐3 also regulates alternative splicing in response to T‐cell receptor activation, and recent phosphoproteomic studies have revealed that multiple splicing factors and regulators of RNA biosynthesis are phosphorylated in a GSK‐3‐dependent manner. Furthermore, inhibition of GSK‐3 alters the splicing of hundreds of mRNAs, indicating a broad role for GSK‐3 in the regulation of RNA processing. GSK‐3‐regulated phosphoproteins include SF3B1, SRSF2, PSF, RBM8A, nucleophosmin 1 (NPM1), and PHF6, many of which are mutated in leukemia and myelodysplasia. As GSK‐3 is inhibited by pathways that are pathologically activated in leukemia and loss of Gsk3 in hematopoietic cells causes a severe myelodysplastic neoplasm in mice, these findings strongly implicate GSK‐3 as a critical regulator of mRNA processing in normal and malignant hematopoiesis.This article is categorized under:
RNA Processing > Splicing Mechanisms
RNA Processing > Splicing Regulation/Alternative Splicing
RNA in Disease and Development > RNA in Disease
RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications
Holomorphic curves in Shimura varieties
Authors: Giacomini Michele 
Published: August 2018

Abstract
We prove a hyperbolic analogue of the Bloch–Ochiai theorem about the Zariski closure of holomorphic curves in abelian varieties. We consider the case of non compact Shimura varieties completing the proof of the result for all Shimura varieties. The statement which we consider here was first formulated and proven by Ullmo and Yafaev for compact Shimura varieties.
Engineering Yarrowia lipolytica for the production of cyclopropanated fatty acids
Authors: Markham Kelly A , Alper Hal S 
Published: August 2018

Abstract
Traditional synthesis of biodiesel competes with food sources and has limitations with storage, particularly due to limited oxidative stability. Microbial synthesis of lipids provides a platform to produce renewable fuel with improved properties from various renewable carbon sources. Specifically, biodiesel properties can be improved through the introduction of a cyclopropane ring in place of a double bond. In this study, we demonstrate the production of C19 cyclopropanated fatty acids in the oleaginous yeast Yarrowia lipolytica through the heterologous expression of the Escherichia coli cyclopropane fatty acid synthase. Ultimately, we establish a strain capable of 3.03 ± 0.26 g/L C19 cyclopropanated fatty acid production in bioreactor fermentation where this functionalized lipid comprises over 32% of the total lipid pool. This study provides a demonstration of the flexibility of lipid metabolism in Y. lipolytica to produce specialized fatty acids.
Evaluating combinations of diagnostic tests to discriminate different dementia types
Authors: Bruun Marie , Rhodius‐Meester Hanneke F.M. , Koikkalainen Juha , Baroni Marta , Gjerum Le , Lemstra Afina W. , Barkhof Frederik , Remes Anne M. , Urhemaa Timo , Tolonen Antti , Rueckert Daniel , van Gils Mark , Frederiksen Kristian S. , Waldemar Gunhild , Scheltens Philip , Mecocci Patrizia , Soininen Hilkka , Lötjönen Jyrki , Hasselbalch Steen G. , van der Flier Wiesje M. 
Published: August 2018

AbstractIntroductionWe studied, using a data‐driven approach, how different combinations of diagnostic tests contribute to the differential diagnosis of dementia.MethodsIn this multicenter study, we included 356 patients with Alzheimer's disease, 87 frontotemporal dementia, 61 dementia with Lewy bodies, 38 vascular dementia, and 302 controls. We used a classifier to assess accuracy for individual performance and combinations of cognitive tests, cerebrospinal fluid biomarkers, and automated magnetic resonance imaging features for pairwise differentiation between dementia types.ResultsCognitive tests had good performance in separating any type of dementia from controls. Cerebrospinal fluid optimally contributed to identifying Alzheimer's disease, whereas magnetic resonance imaging features aided in separating vascular dementia, dementia with Lewy bodies, and frontotemporal dementia. Combining diagnostic tests increased the accuracy, with balanced accuracies ranging from 78% to 97%.DiscussionDifferent diagnostic tests have their distinct roles in differential diagnostics of dementias. Our results indicate that combining different diagnostic tests may increase the accuracy further.
Improving fluoroquinolone use in the outpatient setting using a patient safety initiative
Authors: Jindai Kazuaki , Goto Michihiko , MacKay Kimberly , Forrest Graeme N. , Musuuza Jackson , Safdar Nasia , Pfeiffer Christopher D. 
Published: August 2018

AbstractWe analyzed the impact of a fluoroquinolone patient safety initiative on the weekly fluoroquinolone prescription rate in Veterans Affairs community-based outpatient clinics. We observed a significant initial but unsustained reduction. Such an initiative can function as an antimicrobial stewardship intervention; however, strategies to promote sustainability should be explored.