bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between lifetime coffee consumption and late life cerebral white matter hyperintensities in cognitively normal elderly individuals
Authors: Park Jeongbin , Han Ji Won , Lee Ju Ri , Byun Seonjeong , Suh Seung Wan , Kim Jae Hyoung , Kim Ki Woong 
Published: January 2020

AbstractCoffee consumption is associated with cerebral hypoperfusion that may contribute to the development of cerebral white matter hyperintensities (WMH). We investigated the effect of lifetime coffee consumption on the volume of WMH (VWMH) in late life, and compared the effect between men and women since caffeine clearance may be different between sexes. We enrolled 492 community-dwelling cognitively normal elderly individuals (73.4 ± 6.7 years old on average) from the Korean Longitudinal Study on Cognitive Aging and Dementia. We evaluated their patterns and amounts of coffee consumption using a study-specific standardized interview and estimated cerebral VWMH by automatic segmentation of brain fluid-attenuated inversion recovery sequence magnetic resonance images. Higher cumulative lifetime coffee consumption was associated with higher logVWMH in both sexes (p = 0.030). The participants who consumed more than 2 cups of coffee per day on average in their lifetime showed higher logVWMH in late life than those who consumed less. When both sexes were analyzed separately, these coffee-logVWMH associations were found only in women, although the volumes of brain and white matter of women were smaller than those of men. Our findings suggest that prolonged high coffee consumption may be associated with the risk of WMH in late life.
A Boolean Model of Microvascular Rarefaction to Predict Treatment Outcomes in Renal Disease
Authors: Williams Erika , Chade Alejandro R. 
Published: January 2020

AbstractDespite advances in renovascular disease (RVD) research, gaps remain between experimental and clinical outcomes, translation of results, and the understanding of pathophysiological mechanisms. A predictive tool to indicate support (or lack of) for biological findings may aid clinical translation of therapies. We created a Boolean model of RVD and hypothesized that it would predict outcomes observed in our previous studies using a translational swine model of RVD. Our studies have focused on developing treatments to halt renal microvascular (MV) rarefaction in RVD, a major feature of renal injury. A network topology of 20 factors involved in renal MV rarefaction that allowed simulation of 5 previously tested treatments was created. Each factor was assigned a function based upon its interactions with other variables and assumed to be “on” or “off”. Simulations of interventions were performed until outcomes reached a steady state and analyzed to determine pathological processes that were activated, inactivated, or unchanged vs. RVD with no intervention. Boolean simulations mimicked the results of our previous studies, confirming the importance of MV integrity on treatment outcomes in RVD. Furthermore, our study supports the potential application of a mathematical tool to predict therapeutic feasibility, which may guide the design of future studies for RVD.
Tradeoffs between dispersal and reproduction at an invasion front of cane toads in tropical Australia
Authors: Kelehear Crystal , Shine Richard 
Published: January 2020

AbstractIndividuals at the leading edge of a biological invasion experience novel evolutionary pressures on mating systems, due to low population densities coupled with tradeoffs between reproduction and dispersal. Our dissections of >1,200 field-collected cane toads (Rhinella marina) at a site in tropical Australia reveal rapid changes in morphological and reproductive traits over a three-year period after the invaders first arrived. As predicted, individuals with dispersal-enhancing traits (longer legs, narrower heads) had reduced reproductive investment (lower gonad mass). Post-invasion, the population was increasingly dominated by individuals with less dispersive phenotypes and a higher investment into reproduction (including, increased expression of sexually dimorphic traits in males). These rapid shifts in morphology and reproductive biology emphasise the impacts of the invasion process on multiple, interlinked aspects of organismal biology.
Comprehensive analysis of circRNAs from cashmere goat skin by next generation RNA sequencing (RNA-seq)
Authors: Zheng Yuanyuan , Hui Taiyu , Yue Chang , Sun Jiaming , Guo Dan , Guo Suling , Guo Suping , Li Bojiang , Wang Zeying , Bai Wenlin 
Published: January 2020

AbstractCircular RNA (circRNA) is endogenous non-coding RNA (ncRNA) with a covalently closed circular structure. It is mainly generated through RNA alternative splicing or back-splicing. CircRNA is known in the majority of eukaryotes and very stable. However, knowledge of the circRNA involved in regulating cashmere fineness is limited. Skin samples were collected from Liaoning cashmere goats (LCG) and Inner Mongolia cashmere goats (MCG) during the anagen period. For differentially expressed circRNAs, RNA sequencing was performed, and the analysis led to an identification of 17 up-regulated circRNAs and 15 down-regulated circRNAs in LCG compared with MCG skin samples. In order to find the differentially expressed circRNAs in LCG, we carried out qPCRs on 10 candidate circRNAs in coarse type skin of LCG (CT-LCG) and fine type skin of LCG (FT-LCG). Four circRNAs: ciRNA128, circRNA6854, circRNA4154 and circRNA3620 were confirmed to be significantly differential expression in LCG. Also, a regulatory network of circRNAs-miRNAs was bioinformatically deduced and may help to understand molecular mechanisms of potential circRNA involvement in regulating cashmere fineness.
Morphological Neural Computation Restores Discrimination of Naturalistic Textures in Trans-radial Amputees
Authors: Mazzoni Alberto , Oddo Calogero M. , Valle Giacomo , Camboni Domenico , Strauss Ivo , Barbaro Massimo , Barabino Gianluca , Puddu Roberto , Carboni Caterina , Bisoni Lorenzo , Carpaneto Jacopo , Vecchio Fabrizio , Petrini Francesco M. , Romeni Simone , Czimmermann Tamas , Massari Luca , di Iorio Riccardo , Miraglia Francesca , Granata Giuseppe , Pani Danilo , Stieglitz Thomas , Raffo Luigi , Rossini Paolo M. , Micera Silvestro 
Published: January 2020

AbstractHumans rely on their sense of touch to interact with the environment. Thus, restoring lost tactile sensory capabilities in amputees would advance their quality of life. In particular, texture discrimination is an important component for the interaction with the environment, but its restoration in amputees has been so far limited to simplified gratings. Here we show that naturalistic textures can be discriminated by trans-radial amputees using intraneural peripheral stimulation and tactile sensors located close to the outer layer of the artificial skin. These sensors exploit the morphological neural computation (MNC) approach, i.e., the embodiment of neural computational functions into the physical structure of the device, encoding normal and shear stress to guarantee a faithful neural temporal representation of stimulus spatial structure. Two trans-radial amputees successfully discriminated naturalistic textures via the MNC-based tactile feedback. The results also allowed to shed light on the relevance of spike temporal encoding in the mechanisms used to discriminate naturalistic textures. Our findings pave the way to the development of more natural bionic limbs.
Targeting Forward and Reverse EphB4/EFNB2 Signaling by a Peptide with Dual Functions
Authors: Xiong Chiyi , Wen Yunfei , Zhao Jun , Yin Dengke , Xu Lingyun , Chelariu-Raicu Anca , Yao Cody , Leng Xiaohong , Liu Jinsong , Chaudhari Rajan R. , Zhang Shuxing , Sood Anil K. , Li Chun 
Published: January 2020

AbstractThe tyrosine kinase receptor EphB4 is frequently overexpressed in ovarian and other solid tumors and is involved in interactions between tumor cells and the tumor microenvironment, contributing to metastasis. Trans-interaction between EphB4 and its membrane-bound ligand ephrin B2 (EFNB2) mediates bi-directional signaling: forward EFNB2-to-EphB4 signaling suppresses tumor cell proliferation, while reverse EphB4-to-EFNB2 signaling stimulates the invasive and angiogenic properties of endothelial cells. Currently, no small molecule–based, dual-function, EphB4-binding peptides are available. Here, we report our discovery of a bi-directional ephrin agonist peptide, BIDEN-AP which, when selectively internalized via receptor-mediated endocytosis, suppressed invasion and epithelial-mesenchymal transition of ovarian cancer cells. BIDEN-AP also inhibited endothelial migration and tube formation. In vivo, BIDEN-AP and its nanoconjugate CCPM-BIDEN-AP significantly reduced growth of orthotopic ovarian tumors, with CCPM-BIDEN-AP displaying greater antitumor potency than BIDEN-AP. Both BIDEN-AP and CCPM-BIDEN-AP compromised angiogenesis by downregulating epithelial-mesenchymal transition and angiogenic pathways. Thus, we report a novel EphB4-based therapeutic approach against ovarian cancer.
The influence of predation risk on mate signaling and mate choice in the lesser waxmoth Achroia grisella
Authors: Edomwande Christopher , Barbosa Flavia 
Published: January 2020

AbstractMating signals are often conspicuous and can be eavesdropped on by predators. Therefore, it is expected that predation risk will shape the evolution of sexual communication in both senders and receivers. Males of the lesser waxmoth Achroia grisella produce ultrasonic signals to attract females, and females have preferences for certain signal traits. When they detect predator cues such as bat echolocation calls, males typically stop signaling and females freeze. Here we examine different ways in which predation risk affects male signaling and female choice. We exposed calling males to predator cues under three different treatments: in isolation, within a simulated lek composed of attractive males, or within a simulated lek of unattractive males. We also tested if female choice depends on predation risk by submitting females to a two-choice test between an attractive and an unattractive signal, in the presence and the absence of predator cues. We found that risk-taking behavior is not only impacted by the presence of competitors, but by the competitors’ attractiveness as well. Additionally, more attractive males take more risks when calling in isolation, but not when lekking. In females, we found that preference for the more attractive call disappeared when the attractive call was associated with higher predation risk. These results reinforce the trade-off between traits that increase survival and mate attraction, and bring new insight into the evolution of leks in this species.
Clinical relevance of somatic mutations in main driver genes detected in gastric cancer patients by next-generation DNA sequencing
Authors: Nemtsova Marina V. , Kalinkin Alexey I. , Kuznetsova Ekaterina B. , Bure Irina V. , Alekseeva Ekaterina A. , Bykov Igor I. , Khorobrykh Tatiana V. , Mikhaylenko Dmitry S. , Tanas Alexander S. , Kutsev Sergey I. , Zaletaev Dmitry V. , Strelnikov Vladimir V. 
Published: January 2020

AbstractSomatic mutation profiling in gastric cancer (GC) enables main driver mutations to be identified and their clinical and prognostic value to be evaluated. We investigated 77 tumour samples of GC by next-generation sequencing (NGS) with the Ion AmpliSeq Hotspot Panel v2 and a custom panel covering six hereditary gastric cancer predisposition genes (BMPR1A, SMAD4, CDH1, TP53, STK11 and PTEN). Overall, 47 somatic mutations in 14 genes were detected; 22 of these mutations were novel. Mutations were detected most frequently in the CDH1 (13/47) and TP53 (12/47) genes. As expected, somatic CDH1 mutations were positively correlated with distant metastases (p = 0.019) and tumours with signet ring cells (p = 0.043). These findings confirm the association of the CDH1 mutations with diffuse GC type. TP53 mutations were found to be significantly associated with a decrease in overall survival in patients with Lauren diffuse-type tumours (p = 0.0085), T3-T4 tumours (p = 0.037), and stage III-IV tumours (p = 0.013). Our results confirm that the detection of mutations in the main driver genes may have a significant prognostic value for GC patients and provide an independent GC-related set of clinical and molecular genetic data.
The role of DOT1L in the proliferation and prognosis of gastric cancer
Authors: Song Zaozhi , Wei Zhuoli , Wang Qingkang , Zhang Xinxin , Tao Xiaoying , Wu Nan , Liu Xue , Qian Jun 
Published: January 2020

Abstract
Background: Disruptor of telomeric silencing-1-like (DOT1L), a methyltransferase of H3K79, was observed to be amplified and overexpressed in certain malignancies. This work was aimed at investigating the differences in DOT1L expression and its regulatory mechanism in gastric cancer (GC) and healthy samples.
Methods: Immunohistochemistry was used to detect DOT1L levels in 101 cases of GC and marching adjacent normal tissues. DOT1L was inhibited by small interfering RNA (siRNA) and EPZ5676; a targeting drug. The ability of cells to proliferate were checked by cell counting kit-8 (CCK-8) and clone formation assays, with flow cytometry for observing the cell cycle. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot revealed the gene and protein profiles. Finally, the outcome of EPZ5676 administration was checked on a murine model.
Results: The expression of DOT1L is significantly increased in gastric malignant tumors that is related to the degree of differentiation, lymph node metastasis and TNM staging. DOT1L serves as an independent marker for the prognosis of overall survival (OS) with high levels implying worse prognosis. In addition, DOT1L regulates cyclin-dependent kinase (CDK) 4 (CDK4) and CDK6 through H3K79me2, which leads to a change in the cell cycle at G1, thereby affecting the proliferation of tumors in vitro and in vivo.
Conclusions: This is a first clinical demonstration of the applicability of DOT1L overexpression in gastric tumors. The work is suggestive of altered proliferation of cells by DOT1L via regulating cyclins and H3K79 methylation. This indicates the role of DOT1L in the prognosis and possible medical intervention of GC.
Development of Phonetic Contrasts in Cantonese Tone Acquisition
Authors: Mok Peggy Pik Ki , Li Vivian Guo , Fung Holly Sze Ho 
Published: January 2020

Purpose
Previous studies showed both early and late acquisition of Cantonese tones based on transcription data using different criteria, but very little acoustic data were reported. Our study examined Cantonese tone acquisition using both transcription and acoustic data, illustrating the early and protracted aspects of Cantonese tone acquisition.

Method
One hundred fifty-nine Cantonese-speaking children aged between 2;1 and 6;0 (years;months) and 10 reference speakers participated in a tone production experiment based on picture naming. Natural production materials with 30 monosyllabic words were transcribed by two native judges. Acoustic measurements included overall tonal dispersion and specific contrasts between similar tone pairs: ratios of average fundamental frequency height for the level tones (T1, T3, T6), magnitude of rise and inflection point for the rising tones (T2, T5), magnitude of fall, H1*–H2*, and harmonic-to-noise ratio for the low tones (T4, T6). Auditory assessment of creakiness for T4 was also included.

Results
Children in the eldest group (aged 5;7–6;0) were still not completely adultlike in production accuracy, although two thirds of them had production accuracy over 90%. Children in all age groups had production accuracy significantly higher than chance level, and they could produce the major acoustic contrasts between specific tone pairs similarly as reference speakers. Fine phonetic detail of the inflection point and creakiness was more challenging for children.

Conclusion
Our findings illustrated the multifaceted aspects (both early and late) of Cantonese tone acquisition and called for a wider perspective on how to define successful phonological acquisition.

Supplemental Material

https://doi.org/10.23641/asha.11594853
Automated Acoustic Analysis of Oral Diadochokinesis to Assess Bulbar Motor Involvement in Amyotrophic Lateral Sclerosis
Authors: Rong Panying 
Published: January 2020

PurposeThe purpose of this article was to validate a novel acoustic analysis of oral diadochokinesis (DDK) in assessing bulbar motor involvement in amyotrophic lateral sclerosis (ALS).MethodAn automated acoustic DDK analysis was developed, which filtered out the voice features and extracted the envelope of the acoustic waveform reflecting the temporal pattern of syllable repetitions during an oral DDK task (i.e., repetitions of /tɑ/ at the maximum rate on 1 breath). Cycle-to-cycle temporal variability (cTV) of envelope fluctuations and syllable repetition rate (sylRate) were derived from the envelope and validated against 2 kinematic measures, which are tongue movement jitter (movJitter) and alternating tongue movement rate (AMR) during the DDK task, in 16 individuals with bulbar ALS and 18 healthy controls. After the validation, cTV, sylRate, movJitter, and AMR, along with an established clinical speech measure, that is, speaking rate (SR), were compared in their ability to (a) differentiate individuals with ALS from healthy controls and (b) detect early-stage bulbar declines in ALS.ResultscTV and sylRate were significantly correlated with movJitter and AMR, respectively, across individuals with ALS and healthy controls, confirming the validity of the acoustic DDK analysis in extracting the temporal DDK pattern. Among all the acoustic and kinematic DDK measures, cTV showed the highest diagnostic accuracy (i.e., 0.87) with 80% sensitivity and 94% specificity in differentiating individuals with ALS from healthy controls, which outperformed the SR measure. Moreover, cTV showed a large increase during the early disease stage, which preceded the decline of SR.ConclusionsThis study provided preliminary validation of a novel automated acoustic DDK analysis in extracting a useful measure, namely, cTV, for early detection of bulbar ALS. This analysis overcame a major barrier in the existing acoustic DDK analysis, which is continuous voicing between syllables that interferes with syllable structures. This approach has potential clinical applications as a novel bulbar assessment.
Linguistic Maze Production by Children and Adolescents With Attention-Deficit/Hyperactivity Disorder
Authors: Bangert Katherine J. , Finestack Lizbeth H. 
Published: January 2020

Purpose

Previous investigations reveal that children with attention-deficit/hyperactivity disorder (ADHD) produce elevated rates of linguistic mazes (i.e., filled pauses, repetitions, revisions, and/or abandoned utterances) in expressive language samples (
Redmond, 2004
). The current study aimed to better understand maze use of children and adolescents with ADHD with a focus on the specific maze types produced in different language sampling contexts based on the Autism Diagnostic Observation Schedule (ADOS-2;
Lord et al., 2012
).

Method

Participants included twenty-five 4- to 13-year-olds with a confirmed diagnosis of ADHD. Each participant completed the ADOS to provide narrative and conversational language samples. Research assistants transcribed at least 100 utterances from the ADOS using Systematic Analysis of Language Transcripts (
Miller & Chapman, 2000
) conventions. Dependent variables included the rates of repetitions, revisions, filled pauses, content mazes (
Thordardottir & Ellis Weismer, 2002
), and stalls (
Rispoli, 2003
;
Rispoli, Hadley, & Holt, 2008
) produced in narrative and conversational portions of the ADOS.

Results

In the full sample, participants produced a significantly greater rate of revisions than filled pauses (
p
= .01) and repetitions (
p
< .01). Participants also produced a significantly lower rate of filled pauses than content mazes (
p
< .01). Across contexts, participants produced a higher rate of filled pauses in conversational versus narrative contexts. Age was positively correlated with revisions and content mazes. Mean length of utterance was positively correlated with revisions, repetitions, and context mazes. Expressive language ability was positively correlated with filled pauses and stalls.

Conclusion
The children and adolescents in our sample demonstrated a unique profile of maze use. Sampling context had a limited influence on maze use, whereas maze use was impacted by age, mean length of utterance, and expressive language ability. Study findings highlight the importance of analyzing maze types separately rather than as a single category.
Analysis and development of an electromagnetic exposure map based in spatial interpolation
Authors: de Andrade H.D. , de Figuêiredo A.L. , Fialho B.R. , da S. Paiva J.L. , Queiroz Júnior I. de S. , Sousa M.E.T. 
Published: January 2020

The increasing demand for electricity has led humans to a growing exposure to artificial sources of electromagnetic emission, making it essential to determine the intensity of electromagnetic fields (EMFs), which is subject to the population of a given area. This Letter proposes an analysis of EMF exposure levels and spatial distribution over the region of the input and power circuits of a 230 kV/60 Hz air‐insulated substation. For this, measurement protocols were determined based on current standards and from spatial interpolation methods, a contour map was developed, allowing a complete evaluation of the behaviour and levels of EMF throughout the region. The results obtained indicate that exposure levels in this region are below those recommended by regulatory agencies.
Modulated rapid load pull system for the emulation of envelope tracking power amplifiers
Authors: Alsahali S. , Gecan D. , Alt A. , Chen P. , Woodington S. , Sheikh A. , Tasker P. , Lees J. 
Published: January 2020

This Letter presents a novel characterisation system that is able to fully emulate a complete envelope tracking power amplifier (ET‐PA) environment, with modulated impedance synthesis and dynamic supply voltage generation while using industry‐standard modulated signals and digital pre‐distortion. The system is used to characterise a 10 W GaN device and provide impedance control over the signal and distortion bandwidths, in response to a 10 MHz long‐term evolution signal. A National Instruments PXI‐based measurement system is utilised to apply tracking signals to a bespoke supply modulator and successfully improve the average power added efficiency by ∼18 percentage points. Three different shaping functions are implemented, and their efficiency and linearity performance evaluated. In addition, digital pre‐distortion (DPD) is used to linearise the PA while operating with the three different tracking trajectories. Experimental results demonstrate that when applying shaping functions, a trade‐off needs to be made between efficiency and linearity. Even though a constant gain shaping function provides lower efficiency, it achieves good raw linearity performance without DPD, which is a good option if local linearisation is not available. This novel system is a useful tool in the design of ET‐PAs, to more completely investigate the performance of the device.