bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genospecies of Borrelia burgdorferi sensu lato detected in 16 mammal species and questing ticks from northern Europe
Authors: Mysterud Atle , Stigum Vetle M. , Jaarsma Ryanne I. , Sprong Hein 
Published: March 2019

AbstractLyme borreliosis is the most common vector-borne zoonosis in the northern hemisphere, and the pathogens causing Lyme borreliosis have distinct, incompletely described transmission cycles involving multiple host groups. The mammal community in Fennoscandia differs from continental Europe, and we have limited data on potential competent and incompetent hosts of the different genospecies of Borrelia burgdorferi sensu lato (sl) at the northern distribution ranges where Lyme borreliosis is emerging. We used qPCR to determine presence of B. burgdorferi sl in tissue samples (ear) from 16 mammalian species and questing ticks from Norway, and we sequenced the 5S–23 S rDNA intergenic spacer region to determine genospecies from 1449 qPCR-positive isolates obtaining 423 sequences. All infections coming from small rodents and shrews were linked to the genospecies B. afzelii, while B. burgdorferi sensu stricto (ss) was only found in red squirrels (Sciurus vulgaris). Red squirrels were also infected with B. afzelii and B. garinii. There was no evidence of B. burgdorferi sl infection in moose (Alces alces), red deer (Cervus elaphus) or roe deer (Capreolus capreolus), confirming the role of cervids as incompetent hosts. In infected questing ticks in the two western counties, B. afzelii (67% and 75%) dominated over B. garinii (27% and 21%) and with only a few recorded B. burgdorferi ss and B. valaisiana. B. burgdorferi ss were more common in adult ticks than in nymphs, consistent with a reservoir in squirrels. Our study identifies potential competent hosts for the different genospecies, which is key to understand transmission cycles at high latitudes of Europe.
Molecular dynamics of C99-bound γ-secretase reveal two binding modes with distinct compactness, stability, and active-site retention: implications for Aβ production
Authors: Dehury Budheswar , Tang Ning , Kepp Kasper P. 
Published: March 2019

Abstract
The membrane protease γ-secretase cleaves the C99 fragment of the amyloid precursor protein, thus producing the Aβ peptides central to Alzheimer's disease. Cryo-electron microscopy has provided the topology but misses the membrane and loop parts that contribute to substrate binding. We report here an essentially complete atomic model of C99 within wild-type γ-secretase that respects all the experimental constraints and additionally describes loop, helix, and C99 substrate dynamics in a realistic all-atom membrane. Our model represents the matured auto-cleaved state required for catalysis. From two independent 500-ns molecular dynamic simulations, we identify two conformation states of C99 in equilibrium, a compact and a loose state. Our simulations provide a basis for C99 processing and Aβ formation and explain the production of longer and shorter Aβ, as the compact state retains C99 for longer and thus probably trims to shorter Aβ peptides. We expect pathogenic presenilin mutations to stabilize the loose over the compact state. The simulations detail the role of the Lys53–Lys54–Lys55 anchor for C99 binding, a loss of helicity of bound C99, and positioning of Thr48 and Leu49 leading to alternative trimming pathways on opposite sides of the C99 helix in three amino acid steps. The C99 binding topology resembles that of C83-bound γ-secretase without membrane but lacks a presenilin 1-C99 β-sheet, which could be induced by C83's stronger binding. The loose state should be selectively disfavored by γ-secretase modulators to increase C99 trimming and reduce the formation of longer Aβ, a strategy that is currently much explored but has lacked a structural basis.
FAM83D is associated with gender, AJCC stage, overall survival and disease-free survival in hepatocellular carcinoma
Authors: Liu Xuling , Gao Hong , Zhang Jie , Xue Dongying 
Published: March 2019

Abstract
Prognostic significance of family with sequence similarity 83, member D (FAM83D) in hepatocellular carcinoma (HCC) patients has not been well-investigated using Gene Expression Omnibus (GEO) series and TCGA database, we compared FAM83D expression levels between tumor and adjacent tissues, and correlated FAM83D in tumors with outcomes and clinico-pathological features in HCC patients. Validated in GSE33006, GSE45436, GSE84402 and TCGA, FAM83D was significantly overexpressed in tumor tissues than that in adjacent tissues (all P&lt;0.01). FAM83D up-regulation was significantly associated with worse overall survival (OS) and disease-free survival (DFS) in HCC patients (Log rank P=0.00583 and P=4.178E-04, respectively). Cox analysis revealed that FAM83D high expression was significantly associated with OS in HCC patients [hazard ratio (HR) = 1.44, 95% confidence interval (CI) = 1.005–2.063, P=0.047]. Additionally, patients deceased or recurred/progressed had significantly higher FAM83D mRNA levels than those living or disease-free (P=0.0011 and P=0.0238, respectively). FAM83D high expression group had significantly more male patients and advanced American Joint Committee on Cancer (AJCC) stage cases (P=0.048 and P=0.047, respectively). FAM83D mRNA were significantly overexpressed in male (P=0.0193). Compared with patients with AJCC stage I, those with AJCC stage II and stage III–IV had significantly higher FAM83D mRNA levels (P = 0.0346 and P=0.0045, respectively). In conclusion, overexpressed in tumors, FAM83D is associated with gender, AJCC stage, tumor recurrence and survival in HCC.
Chromatin target of protein arginine methyltransferase regulates invasion, chemoresistance, and stemness in epithelial ovarian cancer
Authors: Feng Xiaojie , Li Lei , Wang Li , Luo Suxia , Bai Xupeng 
Published: March 2019

Abstract
Ovarian cancer is one of the most common gynecological cancers with a high mortality rate in females. Chromatin target of protein arginine methyltransferase (CHTOP) is an important intracellular protein that regulates the transcriptional activation of several oncogenic genes in glioblastomagenesis and controls mature mRNA export as a component of TRanscription-Export complex. However, the role of CHTOP in ovarian cancer is unclear. In the present study, we investigated the correlation between tumor-derived CHTOP expression and prognosis and explored its role in the malignant behaviors of epithelial ovarian cancer cells. We found that higher expression of CHTOP was associated with a lower disease-free survival (DFS) rate in ovarian cancer patients. Also, CHTOP was highly expressed in human ovarian cancer tissues compared with normal and adjacent tissues. Moreover, compared with IGROV-1 cell line, higher expression of CHTOP was also confirmed in the malignant ovarian cancer cell lines (OV-90 and SK-OV-3). Further results from wound-healing and Matrigel assay showed that CHTOP knockdown significantly reduced the migration and invasion ability of OV-90 and SK-OV-3 cells, while colony formation assay and apoptosis detection showed that CHTOP knockdown markedly sensitized OV-90 and SK-OV-3 cells to cisplatin treatment by inducing apoptosis. Additionally, CHTOP silence also remarkably weakened the stemness of OV-90 and SK-OV-3 through inhibiting the protein expressions of several transcriptional or surface markers of cancer stem cells. These findings first suggest that CHTOP, as a highly expressed protein in ovarian cancer, is closely associated with the malignant phenotypes of epithelial ovarian cancer cells, including metastasis, chemoresistance, and stemness, which highlights a promising role of CHTOP in ovarian cancer targeted therapy.
Harmine suppresses bladder tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis
Authors: Hai-rong Cai , Xiang Huang , Xiao-rong Zhang 
Published: March 2019

Abstract
Angiogenesis is a vital step during the process of oncogenesis of a lot of tumors, with no exception in bladder cancer. One of the useful strategies for the development of new drugs against cancer is targeting angiogenesis. In the present study, we found that a small-molecule natural product, which belonged to the β-carboline alkaloid, named harmine, could strongly inhibit tumor angiogenesis thus exhibiting its ideal treatment efficacy in bladder cancer. In vivo study verified that harmine had the effect of inhibition on human bladder tumor xenograft growth. The inhibitory effect of harmine to bladder cancer growth was coordinated by the effects shown on angiogenesis. To further explore the pharmacological activities of harmine, we tested harmine’s influence on blood vessel formation and found that harmine effectively blocked the microvessel sprouting in rat aortic ring assay when stimulated by vascular endothelial growth factor (VEGF). Furthermore, harmine inhibited human umbilical vein endothelial cell (HUVEC) proliferation as well as chemotactic motility, and when we treated HUVEC cell with harmine, the formation of capillary-like structures was also restrained. Moreover, harmine induced bladder cancer cell apoptosis through triggering the caspase-dependent apoptotic pathway and the downstream vascular endothelial growth factor receptor 2 (VEGFR2) kinase pathway was down-regulated, thus suppressing tumor development signals. Herein, our study demonstrated that natural product harmine might have potential in curing human bladder tumor because of its pharmacological function on tumor angiogenesis, trigged by VEGFR2 signaling pathways.
Machine Learning Approaches to Analyze Speech-Evoked Neurophysiological Responses
Authors: Xie Zilong , Reetzke Rachel , Chandrasekaran Bharath 
Published: March 2019

Purpose
Speech-evoked neurophysiological responses are often collected to answer clinically and theoretically driven questions concerning speech and language processing. Here, we highlight the practical application of machine learning (ML)–based approaches to analyzing speech-evoked neurophysiological responses.

Method
Two categories of ML-based approaches are introduced: decoding models, which generate a speech stimulus output using the features from the neurophysiological responses, and encoding models, which use speech stimulus features to predict neurophysiological responses. In this review, we focus on (a) a decoding model classification approach, wherein speech-evoked neurophysiological responses are classified as belonging to 1 of a finite set of possible speech events (e.g., phonological categories), and (b) an encoding model temporal response function approach, which quantifies the transformation of a speech stimulus feature to continuous neural activity.

Results
We illustrate the utility of the classification approach to analyze early electroencephalographic (EEG) responses to Mandarin lexical tone categories from a traditional experimental design, and to classify EEG responses to English phonemes evoked by natural continuous speech (i.e., an audiobook) into phonological categories (plosive, fricative, nasal, and vowel). We also demonstrate the utility of temporal response function to predict EEG responses to natural continuous speech from acoustic features. Neural metrics from the 3 examples all exhibit statistically significant effects at the individual level.

Conclusion
We propose that ML-based approaches can complement traditional analysis approaches to analyze neurophysiological responses to speech signals and provide a deeper understanding of natural speech and language processing using ecologically valid paradigms in both typical and clinical populations.
Functional Logistic Mixed-Effects Models for Learning Curves From Longitudinal Binary Data
Authors: Paulon Giorgio , Reetzke Rachel , Chandrasekaran Bharath , Sarkar Abhra 
Published: March 2019

PurposeWe present functional logistic mixed-effects models (FLMEMs) for estimating population and individual-level learning curves in longitudinal experiments.MethodUsing functional analysis tools in a Bayesian hierarchical framework, the FLMEM captures nonlinear, smoothly varying learning curves, appropriately accommodating uncertainty in various aspects of the analysis while also borrowing information across different model layers. An R package implementing our method is available as part of theSupplemental Materials.ResultsApplication to speech learning data fromReetzke, Xie, Llanos, and Chandrasekaran (2018)and a simulation study demonstrate the utility of FLMEM and its many advantages over linear and logistic mixed-effects models.ConclusionThe FLMEM is highly flexible and efficient in improving upon the practical limitations of linear models and logistic linear mixed-effects models. We expect the FLMEM to be a useful addition to the speech, language, and hearing scientist's toolkit.Supplemental Materialhttps://doi.org/10.23641/asha.7822568
The Heterogeneity of Word Learning Biases in Late-Talking Children
Authors: Perry Lynn K. , Kucker Sarah C. 
Published: March 2019

Purpose

The particular statistical approach researchers choose is intimately connected to the way they conceptualize their questions, which, in turn, can influence the conclusions they draw. One particularly salient area in which statistics influence our conclusions is in the context of atypical development. Traditional statistical approaches such as
t
tests or analysis of variance lend themselves to a focus on group differences, downplaying the heterogeneity that exists within so many atypically developing populations. Understanding such variability is important—classification of what a disorder is, an individual's diagnosis, and whether or not a child receives intervention all directly relate to an accurate classification of the disorder and individual's abilities compared to their typically developing peers.

Method
Here, we use word learning biases (i.e., shape and material biases) in late-talking children as a sample case and employ a variety of statistical approaches to compare the conclusions those approaches might warrant.

Results
We argue that advanced statistical approaches, such as mixed-effects regression, can help us make sense of heterogeneity and are more consistent with a modern dimensional view of language disorders.

Conclusions
Accurate characterization of late-talking children (and others at risk for delays) and their prognoses is necessary for accurate diagnosis and implementation of appropriate target interventions. It therefore requires rigorous statistical analyses that can capture and allow for interpretation of the heterogeneity inherent in populations with language delays and disorders.
Fast magnetoacoustic wave trains with time-dependent drivers
Authors: Goddard C. R. , Nakariakov V. M. , Pascoe D. J. 
Published: March 2019

Context. Frequent observations of quasi-periodic rapidly-propagating wave trains in coronal structures have been made in the last decade. The dispersive evolution of fast magnetohydrodynamic waves propagating in coronal waveguides can provide a physical interpretation for many of these observations.
Aims. Previous studies have considered the generation of fast wave trains by impulsive drivers which deposit energy instantaneously. The signatures of dispersively formed wave trains must depend on the temporal nature of the driver. We investigate the effect of varying the temporal width of the driving perturbation.
Methods. 2D magnetohydrodynamic numerical simulations of impulsively generated wave trains in a guiding field-aligned density enhancement were performed with the novel addition of a time-dependant driver.
Results. The final spatial and spectral signatures of the guided wave trains are found to depend strongly on the temporal duration of the initial perturbation. In particular, the wavelength (or frequency) of highest spectral amplitude is found to increase (decrease) with increasing temporal duration, whereas the spectral width decreases. Additionally, the efficiency of generation of fast wave trains is found to decrease strongly with increasing temporal width of the driver, with a cut-off at twice the internal Alfvén crossing time.
Schematherapie
Authors: Schupp Tobias 
Published: March 2019

ZusammenfassungBei der Zusammenarbeit mit Borderline-Patienten kann die Schematherapie eine
große Hilfe sein. Mit der empathischen Unterstützung der Pflegenden soll der
Patient eine gute Eltern-Kind-Beziehung erleben. Wir stellen die Therapieform
vor und erläutern, wie damit die gesunden Anteile des Patienten gestärkt werden
können.
Wound Healing Potential of the Standardized Extract of Boswellia serrata on Experimental Diabetic Foot Ulcer via Inhibition of Inflammatory, Angiogenetic and Apoptotic Markers
Authors: Pengzong Zhang , Yuanmin Li , Xiaoming Xiong , Shang Deng , Wei Xiong , Zhigang Lang , Dongzhou Du , Wenjing Yu , Jianbiao Yue , Yang Xiang , Xia Li 
Published: March 2019

AbstractThe aim of the present study was to evaluate the wound healing potential and possible mechanism of action of the standardized extract of Boswellia serrata against the experimental model of diabetic foot ulcer. α-Boswellic acid was isolated from the standardized extract of B. serrata and characterized (HPLC, 1H-NMR, 13C-NMR, ESI-MS). Diabetes was induced in Sprague-Dawley rats by streptozotocin (55 mg/kg, i. p.), and wounds were created on the dorsal surface of the hind paw. B. serrata (100, 200, and 400 mg/kg, p. o.) was administered to the rats for 16 days. The HPLC analysis showed a single peak with a retention time of 12.51 min. The compound was identified with ESI-MS [M + Na]+ = 455.37 as α-boswellic acid. Treatment with B. serrata (200 and 400 mg/kg) significantly increased the rate of wound contraction via modulation of oxido-nitrosative stress and elevated the hydroxyproline level at the wound area. reverse transcription-PCR analysis revealed that streptozotocin-induced increases in TNF-α, interleukin-1β, interleukin-6, nuclear factor-kappa-light-chain-enhancer of activated B cells, and Bcl-2-associated X protein, and decreases in angiopoietin-1, Tie2, transforming growth factor beta 1, vascular endothelial growth factor, and collagen-1 mRNA expression were significantly inhibited by B. serrata. It also significantly reduced wound cellular necrosis as evaluated by flow cytometry using propidium iodide fluorescence intensity. Streptozotocin-induced histopathological alterations were also significantly ameliorated by B. serrata. In conclusion, standardized extracts of B. serrata exert its wound healing potential via orchestrating mechanisms, which include the inhibition of oxido-inflammatory markers (oxido-nitrosative stress, TNF-α, interleukins, and nuclear factor-kappa-light-chain-enhancer of activated B cells), increased collagen synthesis (hydroxyproline and collagen-1) and angiogenesis (Ang-1/Tie2), promoting growth factors (transforming growth factor beta 1 and vascular endothelial growth factor), and inhibition of apoptosis (Bcl-2-associated X protein) to accelerate wound healing in experimental delayed diabetic foot ulcer.
Novel Targets in the Immune Microenvironment of the Hepatic Sinusoids for Treating Liver Diseases
Authors: Patten Daniel , Shepherd Emma , Weston Christopher , Shetty Shishir 
Published: March 2019

AbstractImmune dysregulation and accumulation of leukocytes is a hallmark of adult chronic liver diseases. Progressive hepatic inflammation can lead to fibrosis and cirrhosis with a high risk of liver failure or hepatocellular cancer (HCC). Recent advances have been made in the treatment of liver disease including the development of highly effective antiviral therapy for hepatitis C and the potential of immunotherapy for HCC. Despite this, the majority of other chronic liver diseases including alcoholic liver disease, fatty liver disease, and cholestatic diseases do not respond to conventional anti-inflammatory therapies. Recent studies defining the organ-specific properties that contribute to resident immune activation and immune cell recruitment from the circulation in these conditions have identified novel hepatic inflammatory pathways, which are now being targeted in clinical trials. Further understanding of how the immune microenvironment is regulated within the liver and how disease-specific mechanisms alter this process will hopefully lead to combination therapies to prevent aberrant inflammation and also promote fibrosis resolution. In this review, we focus on the advances that have been made in identifying key components of the inflammatory pathway including the recognition of danger signals, the recruitment and retention of lymphocytes from the circulation, and the pathways that promote resolution.
Assessing health reform: studying tool appropriateness & critical capacities
Authors: Bali Azad Singh , Ramesh M 
Published: March 2019

AbstractThe past two decades have witnessed unprecedented policy effort to improve access to medical services and strengthen financial protection from catastrophic healthcare expenditure. Despite billions of dollars in health spending, many – especially across the developing world – continue to remain vulnerable to financial impoverishment. What accounts for this poor performance? To respond to this question, we turn to the design literature in public policy, which emphasises the role of policy tools or combination of tools in addressing a social problem. In this paper, we focus on two inter-related aspects of the design orientation to explain outcomes: a) the appropriateness of the policy tool and b) the capacity of government agencies. We apply a framework, which integrates vital questions on both these aspects along three common dimensions (analytical, operational and political) to assess healthcare reforms in India and Thailand. The case studies illustrate the importance of both these aspects of the design orientation in explaining outcomes, and show how they are commonly overlooked in the health and social policy literatures, and in reforms underway.
Thermal block of action potentials is primarily due to voltage-dependent potassium currents: a modeling study
Authors: Ganguly Mohit , Jenkins Michael W , Jansen E Duco , Chiel Hillel J 
Published: March 2019

Abstract

Objective. Thermal block of action potential conduction using infrared lasers is a new modality for manipulating neural activity. It could be used for analysis of the nervous system and for therapeutic applications. We sought to understand the mechanisms of thermal block. Approach. To analyze the mechanisms of thermal block, we studied both the original Hodgkin/Huxley model, and a version modified to more accurately match experimental data on thermal responses in the squid giant axon. Main results. Both the original and modified models suggested that thermal block, especially at higher temperatures, is primarily due to a depolarization-activated hyperpolarization as increased temperature leads to faster activation of voltage-gated potassium ion channels. The minimum length needed to block an axon scaled with the square root of the axon’s diameter. Significance. The results suggest that voltage-dependent potassium ion channels play a major role in thermal block, and that relatively short lengths of axon could be thermally manipulated to selectively block fine, unmyelinated axons, such as C fibers, that carry pain and other sensory information.