bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expanding the neurodevelopmental phenotypes of individuals with de novo KMT2A variants
Authors: Chan Ada J. S. , Cytrynbaum Cheryl , Hoang Ny , Ambrozewicz Patricia M. , Weksberg Rosanna , Drmic Irene , Ritzema Anne , Schachar Russell , Walker Susan , Uddin Mohammed , Zarrei Mehdi , Yuen Ryan K. C. , Scherer Stephen W. 
Published: April 2019

AbstractDe novo loss-of-function (LoF) variants in the KMT2A gene are associated with Wiedemann−Steiner Syndrome (WSS). Recently, de novo KMT2A variants have been identified in sequencing studies of cohorts of individuals with neurodevelopmental disorders (NDDs). However, most of these studies lack the detailed clinical information required to determine whether those individuals have isolated NDDs or WSS (i.e. syndromic NDDs). We performed thorough clinical and neurodevelopmental phenotyping on six individuals with de novo KMT2A variants. From these data, we found that all six patients met clinical criteria for WSS and we further define the neurodevelopmental phenotypes associated with KMT2A variants and WSS. In particular, we identified a subtype of Autism Spectrum Disorder (ASD) in five individuals, characterized by marked rigid, repetitive and inflexible behaviours, emotional dysregulation, externalizing behaviours, but relative social motivation. To further explore the clinical spectrum associated with KMT2A variants, we also conducted a meta-analysis of individuals with KMT2A variants reported in the published literature. We found that de novo LoF or missense variants in KMT2A were significantly more prevalent than predicted by a previously established statistical model of de novo mutation rate for KMT2A. Our genotype−phenotype findings better define the clinical spectrum associated with KMT2A variants and suggest that individuals with de novo LoF and missense variants likely have a clinically unrecognized diagnosis of WSS, rather than isolated NDD or ASD alone. This highlights the importance of a clinical genetic and neurodevelopmental assessment for individuals with such variants in KMT2A.
Mapping the metabolism of five amino acids in bloodstream form Trypanosoma brucei using U-13C-labelled substrates and LC–MS
Authors: Johnston Katharina , Kim Dong-Hyun , Kerkhoven Eduard J. , Burchmore Richard , Barrett Michael P. , Achcar Fiona 
Published: April 2019

Abstract
The metabolism of the parasite Trypanosoma brucei has been the focus of numerous studies since the 1940s. Recently it was shown, using metabolomics coupled with heavy-atom isotope labelled glucose, that the metabolism of the bloodstream form parasite is more complex than previously thought. The present study also raised a number of questions regarding the origin of several metabolites, for example succinate, only a proportion of which derives from glucose. In order to answer some of these questions and explore the metabolism of bloodstream form T. brucei in more depth we followed the fate of five heavy labelled amino acids – glutamine, proline, methionine, cysteine and arginine – using an LC–MS based metabolomics approach. We found that some of these amino acids have roles beyond those previously thought and we have tentatively identified some unexpected metabolites which need to be confirmed and their function determined.
Cardamonin exerts anti-gastric cancer activity via inhibiting LncRNA-PVT1-STAT3 axis
Authors: Wang Zheng , Tang Xiaoli , Wu Xiaoqing , Yang Meiyuan , Wang Wei , Wang Liuhua , Tang Dong , Wang Daorong 
Published: April 2019

Abstract
Background: Gastric cancer is one of the most commonly diagnosed cancers each year, and it remains the third leading cause of cancer death in the world. The clinicopathologic characteristics differ among regions, so epigenetic changes play a key role in gastric carcinogenesis. Methods: In the present study, we first demonstrate that cardamonin, a natural production of chalcone, is an anti-gastric cancer agent in pre-clinical evaluation. Results: Cardamonin inhibited proliferation and migration, induced apoptosis in gastric cancer cells. It could reduce the expression of apoptosis-related and migration-related genes and proteins. The constant activation of STAT3 (signal transducer and activator of transcription 3) signal is a major intrinsic signal for cancer inflammation. It regulates cellular proliferation, cell cycle, and migration that are critical for cancer procession. Cardamonin could effectively down-regulate p-STAT3 and abolish activation of STAT3 through inhibiting the expression of LncRNA-PVT1. Conclusion: The present study revealed that cardamonin is a potential natural source of anti-gastric cancer drugs via epigenetic mechanism to inhibit LncRNA-PVT1-STAT3 axis.
Effects of Aging on Perceptual and Electrophysiological Responses to Acoustic Pulse Trains as a Function of Rate
Authors: Gaskins Casey , Jaekel Brittany N. , Gordon-Salant Sandra , Goupell Matthew J. , Anderson Samira 
Published: April 2019

Purpose
As pulse rate increases beyond a few hundred Hertz, younger normal-hearing (NH) participants' ability to encode temporal information in band-limited acoustic pulse trains decreases, demonstrating a rate limitation in processing rapid temporal information. Rate discrimination abilities, however, have yet to be investigated in older NH participants—a population that experiences age-related temporal processing deficits. It was hypothesized that age-related temporal processing deficits lead to decreased temporal rate discrimination abilities in older compared with younger NH participants, which could be observed in both perceptual and electrophysiological measurements.

Method

Fifteen younger and 15 older NH participants were presented acoustic pulse trains with a 4-kHz center frequency and 1-kHz bandwidth at 75 dB SPL monaurally. The pulse rate was 80, 200, or 400 Hz. Just noticeable differences were obtained using an adaptive procedure that instructed the participants to identify the pulse train with the highest pitch. Auditory steady-state responses (ASSRs) were recorded to the same pulse trains with 2 additional rates—20 and 40 Hz. The Digit Symbol Coding and Digit Symbol Search subtests of the Wechsler Adult Intelligence Scale (
Wechsler, 1997
) were measured as correlates to domain-general cognitive processing speed.

Results
As rate increased from 80 to 400 Hz, performance on the perceptual rate discrimination task worsened in both groups. ASSR spectral energy also decreased, but only in the older group. Perceptual performance was equivalent between groups across rates. The older group had lower ASSR spectral energy (lower signal-to-noise ratios) at the 400-Hz rate than the younger group, but there were no group differences for the other rates. The overall strength of neural rate representation, along with speed of processing performance, predicted perceptual performance for the 400-Hz rate.

Conclusion
These results suggest that neural representation at early levels of the auditory system and processing speed are factors in perceptual auditory temporal processing performance, especially in older adults.
The Circle of Care for Older Adults With Hearing Loss and Comorbidities: A Case Study of a Geriatric Audiology Clinic
Authors: Dupuis Kate , Reed Marilyn , Bachmann Florine , Lemke Ulrike , Pichora-Fuller M. Kathleen 
Published: April 2019

Purpose
Older adults seeking audiologic rehabilitation often present with medical comorbidities, yet these realities of practice are poorly understood. Study aims were to examine (a) the frequency of identification of selected comorbidities in clients of a geriatric audiology clinic, (b) the influence of comorbidities on audiology practice, and (c) the effect of comorbidities on rehabilitation outcomes.

Method

The records of 135 clients (
M
age
= 86 years) were examined. Information about comorbidities came from audiology charts (physical paper files) and hospital electronic health records (EHRs). Data about rehabilitation recommendations and outcomes came from the charts. Focus groups with audiologists probed their views of how comorbidities influenced their practice.

Results
The frequency of identification was 68% for visual, 50% for cognitive, and 42% for manual dexterity issues; 84% had more than one comorbidity. Also noted were hypertension (43%), falls (33%), diabetes (13%), and depression (16%). Integrating information from the audiology chart and EHR provided a more complete understanding of comorbidities. Information about hearing in the EHR included logs of outpatient audiology visits (75% of 135 cases), audiologists' care notes for inpatients and long-term care residents (25%), and entries by other health professionals (60%). Modifications to audiology practice were common and varied depending on comorbidity. High rates of success were achieved regardless of comorbidities.

Conclusions
In this clinic, successful outcomes were achieved by modifying audiology practice for clients with comorbidities. Increased interprofessional communication among clinicians in the circle of care could improve care planning and outcomes for older adults with hearing loss.
Observation-based modelling of magnetised coronal mass ejections with EUHFORIA
Authors: Scolini C. , Rodriguez L. , Mierla M. , Pomoell J. , Poedts S. 
Published: April 2019

Context. Coronal mass ejections (CMEs) are the primary source of strong space weather disturbances at Earth. Their geo-effectiveness is largely determined by their dynamic pressure and internal magnetic fields, for which reliable predictions at Earth are not possible with traditional cone CME models.Aims. We study two well-observed Earth-directed CMEs using the EUropean Heliospheric FORecasting Information Asset (EUHFORIA) model, testing for the first time the predictive capabilities of a linear force-free spheromak CME model initialised using parameters derived from remote-sensing observations.Methods. Using observation-based CME input parameters, we performed magnetohydrodynamic simulations of the events with EUHFORIA, using the cone and spheromak CME models.Results. Simulations show that spheromak CMEs propagate faster than cone CMEs when initialised with the same kinematic parameters. We interpret these differences as the result of different Lorentz forces acting within cone and spheromak CMEs, which lead to different CME expansions in the heliosphere. Such discrepancies can be mitigated by initialising spheromak CMEs with a reduced speed corresponding to the radial speed only. Results at Earth provide evidence that the spheromak model improves the predictions ofB(Bz) by up to 12–60 (22–40) percentage points compared to a cone model. Considering virtual spacecraft located within ±10° around Earth,B(Bz) predictions reach 45–70% (58–78%) of the observed peak values. The spheromak model shows inaccurate predictions of the magnetic field parameters at Earth for CMEs propagating away from the Sun-Earth line.Conclusions. The spheromak model successfully predicts the CME properties and arrival time in the case of strictly Earth-directed events, while modelling CMEs propagating away from the Sun-Earth line requires extra care due to limitations related to the assumed spherical shape. The spatial variability of modelling results and the typical uncertainties in the reconstructed CME direction advocate the need to consider predictions at Earth and at virtual spacecraft located around it.
Analysis of the controllability from the exterior of strong damping nonlocal wave equations
Authors: Warma Mahamadi , Zamorano Sebastián 
Published: April 2019

We make a complete analysis of the controllability properties from the exterior of the (possible) strong damping wave equation associated with the fractional Laplace operator subject to the non-homogeneous Dirichlet type exterior condition. In the first part, we show that if 0 <s< 1, Ω ⊂ ℝN(N≥ 1) is a bounded Lipschitz domain and the parameterδ> 0, then there is no control functiongsuch that the following system\begin{align} u_{1,n}+ u_{0,n}\widetilde{\lambda}_{n}^++ \delta u_{0,n}\lambda_{n}=\int_0^{T}\int_{\Omc}(g(x,t)+\delta g_t(x,t))e^{-\widetilde{\lambda}_{n}^+ t}\mathcal{N}_{s}\varphi_{n}(x)\d x\d t,\label{39}\\ u_{1,n}+ u_{0,n}\widetilde{\lambda}_{n}^- +\delta u_{0,n}\lambda_{n}=\int_0^{T}\int_{\Omc}(g(x,t)+\delta g_t(x,t))e^{-\widetilde{\lambda}_{n}^- t}\mathcal{N}_{s}\varphi_{n}(x)\d x\d t,\label{40} \end{align}is exact or null controllable at timeT> 0. In the second part, we prove that for everyδ≥ 0 and 0 <s< 1, the system is indeed approximately controllable for anyT> 0 andg∈D(O× (0,T)), whereO⊂ ℝN\ Ω is any non-empty open set.
Aktuelle Empfehlungen zur Diagnostik der Riesenzellarteriitis
Authors: Bley Thorsten , Zänker Michael , Dechant Claudia , Venhoff Nils 
Published: April 2019

AbstractIn Giant Cell Arteritis (GCA), a timely diagnosis is required to avoid severe complications such as blindness or structural vascular damage. The heterogeneous symptoms are mainly due to local and systemic inflammatory processes. Diagnostics are based on increased inflammation parameters in the laboratory, imaging, in which color-coded duplex sonography (FKDS), high-resolution magnetic resonance imaging (MRI), computer tomography (CT) or CT angiography (CTA) and 18F fluorodeoxyglucose-positron emission tomography with CT (FDG-PET-CT) have become established, as well as histopathological findings in temporal artery biopsy.
Dupilumab-asssoziierte Abheilung einer Alopecia areata bei Atopischem Ekzem
Authors: Aszodi Nora , Pumnea Teodora , Wollenberg Andreas 
Published: April 2019

Zusammenfassung
Anamnese und klinischer Befund Eine 25-jährige Patientin wurde aufgrund eines schweren atopischen Ekzems (AE) mit dem anti IL-4/IL-13-Rezeptor-Antikörper Dupilumab behandelt. Zusätzlich litt die Patientin seit 5 Jahren an einer Alopecia areata (AA).
Untersuchungen und Diagnose Bei Erstvorstellung zeigte die körperliche Untersuchung ein schweres AE (Scoring Atopic Dermatitis [SCORAD] 76,0; Eczema Area and Severity Index [EASI] 37,4) mit einem Gesamt-IgE von 1108 kU/l sowie eine Alopecia areata.
Therapie und Verlauf Vor einem Jahr wurde eine Behandlung mit dem anti IL-4/IL-13-Rezeptor-Antikörper Dupilumab eingeleitet. Nach 5 Monaten zeigte sich eine deutliche Besserung des AE (SCORAD 32,2; EASI 3,8), sowie ein zunehmender Haarwuchs. Nach 11 Monaten Therapiedauer blieb das AE stabil gebessert (SCORAD 27,0; EASI 2,7), zudem waren nahezu alle Haare nachgewachsen.
Folgerung Die Komorbidität zwischen AE und AA ist seit Jahren bekannt, die Beeinflussung der AA durch Dupilumab ist eine neue Erkenntnis. Der vorliegende Fallbericht unterstützt die Hypothese, dass eine Hemmung der IL-4- und IL-13-Signalwege tatsächlich und längerfristig Einfluss auf den Haarwuchs bei AA hat. Bei Patienten mit AE und begleitender AA ist ein positiver Effekt auch auf die Komorbidität AA zu erwarten.
Pharmacology for the Audiologist
Authors: Offerdahl Tracy , Mishra Vallabhi 
Published: April 2019

AbstractThe purpose of this article is to provide a brief introduction and review regarding basic principles of pharmacology, including terminology and colloquialisms, as well as pharmacokinetic and pharmacodynamic principles of ototoxic agents. As an audiology practitioner, it is more important than ever to have a working knowledge regarding the known and proposed mechanisms of action for drugs and chemicals with known ototoxicity potential. Additionally, this article provides a discussion regarding the biochemistry behind distribution, which is a major step in determining ototoxic potential of known and potential ototoxins.
Otoprotectants: From Research to Clinical Application
Authors: Le Prell Colleen 
Published: April 2019

AbstractThere is an urgent need for otoprotective drug agents. Prevention of noise-induced hearing loss continues to be a major challenge for military personnel and workers in a variety of industries despite the requirements that at-risk individuals use hearing protection devices such as ear plugs or ear muffs. Drug-induced hearing loss is also a major quality-of-life issue with many patients experiencing clinically significant hearing loss as a side effect of treatment with life-saving drug agents such as cisplatin and aminoglycoside antibiotics. There are no pharmaceutical agents approved by the United States Food and Drug Administration for the purpose of protecting the inner ear against damage, and preventing associated hearing loss (otoprotection). However, a variety of preclinical studies have suggested promise, with some supporting data from clinical trials now being available as well. Additional research within this promising area is urgently needed.
Orbitocranial Approaches to the Skull Base
Authors: Vincent Aurora , Wang Weitao , Sokoya Mofiyinfolu , Kadakia Sameep , Chan David , Ducic Yadranko 
Published: April 2019

AbstractThere are a myriad of approaches and surgical options for removal and treatment of skull base diseases. While, historically, large open approaches have been preferred, several endoscopic and minimally invasive techniques are now available that preserve intraoperative visualization and surgical success while minimizing morbidity and recovery times. Herein, the authors review common open, minimally invasive, and endoscopic approaches to the anterior skull base.
Roles of action research in the professional development of Chinese language teachers
Authors: Yuan Fangyuan 
Published: April 2019

Abstract
This study examined the roles of action research in the professional development of Chinese language teachers.
Participants were a group of Chinese teachers enrolled in a teacher training course. In light of theories and research,
participants were guided to reflect on their own teaching beliefs and practice and design a research project about their own
teaching. Using a descriptive-explorative design, this study elicited data from multiple sources, including students’ pre-course
survey, professional journals, reflective essays, project reports, group interviews, email exchanges with the instructor, and
instructor’s field notes. Three categories emerged from the data analysis that reflected students’ gains from the process: a
broader conception of research on language teaching and learning, a more sophisticated understanding of foreign language teaching
in general and their own teaching in particular, and a learning process of how to be a teacher-researcher. Contributing and
impeding factors are discussed and values of teacher research are suggested.
Register in historical linguistics
Authors: Kytö Merja 
Published: April 2019

AbstractMerja Kytö is Professor of English Language at Uppsala University. In this article, she provides a detailed accounting of the role of register in research on the historical development of language. Her substantial body of work has focused on both the historical development of specific registers, as well as how historical change has been mediated by register. Her research has encompassed a range of time periods (from Early Modern English to the 19th century) and registers (for example, depositions, Salem witchcraft records, and dialogues). Her many edited collections have brought historical linguists together into comprehensive and rigorous volumes, including theCambridge Handbook of English Historical Linguistics(Kytö & Pahta 2016, Cambridge University Press),English in Transition: Corpus-Based Studies in Linguistic Variation and Genre Styles(Rissanen, Kytö, & Heikkonen 1997, De Gruyter), andDevelopments in English: Expanding Electronic Evidence(Taavitsainen, Kytö, Claridge, & Smith 2014, Cambridge University Press). She has been a key contributor to the development of principled historical corpora, such as theHelsinki Corpus of English Textsproject, which represents a range of registers from Old and Middle English to Early Modern English. Merja Kytö has long been a leader in demonstrating how systematic attention to register can result in rich profiles of historical development, and in addressing the inherent challenges involved in utilizing historical documents for linguistic research.
Abies Mill.
Authors: Savill P. 
Published: April 2019

Abstract

This chapter describes the origin and introduction; climatic and site requirements, and other silvicultural characteristics; pests and diseases; natural regeneration; flowering, seed production and nursery conditions; provenance; timber and uses; yield and timber; and place of the following fir species in British forestry: Abies alba, A. grandis, and A. procera. The chapter also provides details on some species of silver fir that might be useful in a changing climate, including A. borisii-regis, A. cephalonica, A. cilicica, A. nordmanniana, and A. pinsapo. Finally, the chapter explores the likely silvicultural and utilization potential of Southern European Silver Firs in the UK.
Alnus Mill.
Authors: Savill P. 
Published: April 2019

Abstract

This chapter describes the origin and introduction; climatic and site requirements, and other silvicultural characteristics; pests and diseases; natural regeneration; flowering, seed production and nursery conditions; provenance; taxonomy and distribution; timber and uses; yield and timber; and place of the following alder species in British forestry: Alnus cordata, A. glutinosa, A. incana, A. rubra, and A. viridis.
Populus L.
Authors: Savill P. 
Published: April 2019

Abstract

This chapter describes the origin and introduction; climatic and site requirements, and other silvicultural characteristics; pests and diseases; natural regeneration; flowering, seed production and nursery conditions; provenance; yield, timber and uses; and place of poplars (Populus nigra, P. tremula, P. × canadensis and P. × euramericana) in British forestry.
American Society of Clinical Oncology/College of American Pathologists 2018 Focused Update of Breast Cancer HER2 FISH Testing GuidelinesResults From a National Reference Laboratory
Authors: Lin Leo , Sirohi Deepika , Coleman Joshua F , Gulbahce H Evin 
Published: April 2019

AbstractObjectivesTo review impact of the ASCO/CAP 2018 update on HER2 testing.MethodsHER2 fluorescence in situ hybridization (FISH) test requests from primary and metastatic breast cancers between August 2018 and January 2019 were included. FISH results requiring a changed algorithm under the new guidelines (groups 2, 3, and 4) were identified and HER2:CEN17 ratios, average HER2, CEN17 signals/cell, and HER2 immunohistochemistry (IHC) results were recorded.ResultsOf the HER2 FISH cases 176/812(21.7%) fell within groups 2, 3, or 4; 0/12, 1/12, and 2/152 cases were positive (3+) by IHC, and 1/12, 2/12, and 6/152 cases were positive after targeted scoring from groups 2, 3, and 4, respectively. Following 2018 updates, 8.3%, 25%, and 5.3% of the groups 2, 3, and 4 were positive, respectively.ConclusionsGroups 2, 3, and 4 constituted over 20% of HER2 FISH tests in a reference laboratory. The 2018 ASCO/CAP update significantly decreased the HER2 positivity rate.