bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of the transcriptional kinase CDK7 overcomes therapeutic resistance in HER2-positive breast cancers
Authors: Sun Bowen , Mason Seth , Wilson Robert C. , Hazard Starr E. , Wang Yubao , Fang Rong , Wang Qiwei , Yeh Elizabeth S. , Yang Meixiang , Roberts Thomas M. , Zhao Jean J. , Wang Qi 
Published: August 2019

AbstractResistance of breast cancer to human epidermal growth factor receptor 2 (HER2) inhibitors involves reprogramming of the kinome through HER2/HER3 signaling via the activation of multiple tyrosine kinases and transcriptional upregulation. The heterogeneity of induced kinases prevents kinase targeting by a single kinase inhibitor and presents a major challenge to the treatment of therapeutically recalcitrant HER2-positive breast cancers (HER2+ BCs). As a result, there is a critical need for effective treatment that attacks the aberrant kinome activation associated with resistance to HER2-targeted therapy. Here, we describe a novel treatment strategy that targets cyclin-dependent kinase 7 (CDK7) in HER2 inhibitor-resistant (HER2iR) breast cancer. We show that both HER2 inhibitor-sensitive (HER2iS) and HER2iR breast cancer cell lines exhibit high sensitivity to THZ1, a newly identified covalent inhibitor of the transcription regulatory kinase CDK7. CDK7 promotes cell cycle progression through inhibition of transcription, rather than via direct phosphorylation of classical CDK targets. The transcriptional kinase activity of CDK7 is regulated by HER2, and by the receptor tyrosine kinases activated in response to HER2 inhibition, as well as by the downstream SHP2 and PI3K/AKT pathways. A low dose of THZ1 displayed potent synergy with the HER2 inhibitor lapatinib in HER2iR BC cells in vitro. Dual HER2 and CDK7 inhibition induced tumor regression in two HER2iR BC xenograft models in vivo. Our data support the utilization of CDK7 inhibition as an additional therapeutic avenue that blocks the activation of genes engaged by multiple HER2iR kinases.
Adaptation of emotional state and standing balance parameters following repeated exposure to height-induced postural threat
Authors: Zaback Martin , Adkin Allan L. , Carpenter Mark G. 
Published: August 2019

AbstractHeight-induced postural threat influences standing balance control. However, it is unknown if minimizing individuals’ emotional response to threat moderates this relationship. This study repeatedly exposed individuals to height-induced postural threat to determine if reducing the emotional response to threat influences standing balance control. Sixty-eight young adults completed a series of standing trials at LOW (0.8 m above ground, away from edge) and HIGH (3.2 m above ground, at edge) postural threat conditions. Emotional state was assessed using self-report and electrodermal measures. Standing balance was assessed through analysis of centre of pressure (COP) movement and lower leg electromyographic activity. Individuals’ emotional response to threat was attenuated following repeated threat exposure. However, threat-induced changes in standing balance were largely preserved. When initially threatened, individuals leaned backward and demonstrated smaller amplitude and higher frequency of COP adjustments; these balance outcomes did not change following repeated threat exposure. Only high frequency COP oscillations (>1.8 Hz) and ankle muscle co-contraction showed any adaptation; regression analyses showed that these behavioural adaptations were accounted for by a combination of emotional and cognitive state changes. This suggests that some threat-induced standing balance changes are more closely linked with the emotional response to threat than others, and are therefore amendable to intervention.
A novel and simple formula to predict liver mass in porcine experimental models
Authors: Martínez de la Maza Lilia , Prado Verónica , Hessheimer Amelia J. , Muñoz Javier , García-Valdecasas Juan Carlos , Fondevila Constantino 
Published: August 2019

AbstractA primary limitation in hepatic surgery is leaving a remnant liver of adequate size and function. Experimental models have been designed to study processes of liver injury and regeneration in this context, yet a formula to accurately calculate liver mass in an animal model is lacking. This study aims to create a novel and simple formula to estimate the mass of the native liver in a species of pigs commonly used in experimental liver surgery protocols. Using data from 200 male weanling Landrace-Large White hybrid pigs, multiple linear regression analysis is used to generate the formula. Clinical features used as variables for the predictive model are body mass and length. The final formula for pig liver mass is as follows: Liver mass (g) = 26.34232 * Body mass (kg) – 1.270629 * Length (cm) + 163.0076; R2 = 0.7307. This formula for porcine liver mass is simple to use and may be helpful in studies using animals of similar characteristics to evaluate restoration of liver mass following major hepatectomy.
Mitochondrial sub-cellular localization of cAMP-specific phosphodiesterase 8A in ovarian follicular cells
Authors: Lounas Amel , Vernoux Nathalie , Germain Marc , Tremblay Marie-Eve , Richard François J. 
Published: August 2019

AbstractCyclic adenosine monophosphate (cAMP) is a ubiquitous secondary messenger that plays a central role in endocrine tissue function, particularly in the synthesis of steroid hormones. The intracellular concentration of cAMP is regulated through its synthesis by cyclases and its degradation by cyclic nucleotide phosphodiesterases (PDEs). Although the expression and activity of PDEs impact the specificity and the amplitude of the cAMP response, it is becoming increasingly clear that the sub-cellular localization of PDE emphasizes the spatial regulation of the cell signalling processes that are essential for normal cellular function. We first examined the expression of PDE8A in porcine ovarian cells. PDE8A is expressed in granulosa cells, cumulus cells and oocytes. Second, we assessed the mitochondrial sub-cellular localization of PDE8A. Using western blotting with isolated mitochondrial fractions from granulosa cells and cumulus-oocyte complexes revealed immuno-reactive bands. PDE assay of isolated mitochondrial fractions from granulosa cells measured specific PDE8 cAMP-PDE activity as PF-04957325-sensitive. The immune-reactive PDE8A signal and MitoTracker labelling co-localized supporting mitochondrial sub-cellular localization of PDE8A, which was confirmed using immuno-electron microscopy. Finally, the effect of PDE8 on progesterone production was assessed during the in-vitro maturation of cumulus-oocyte complexes. Using PF-04957325, we observed a significant increase (P < 0.05) in progesterone secretion with follicle-stimulating hormone (FSH). Active mitochondria stained with MitoTracker orange CMTMRos were also increased by the specific PDE8 inhibitor supporting its functional regulation. In conclusion, we propose the occurrence of mitochondrial sub-cellular localization of PDE8A in porcine granulosa cells and cumulus cells. This suggests that there is potential for new strategies for ovarian stimulation and artificial reproductive technologies, as well as the possibility for using new media to improve the quality of oocytes.
Beyond 30% Conversion Efficiency in Silicon Solar Cells: A Numerical Demonstration
Authors: Bhattacharya Sayak , John Sajeev 
Published: August 2019

AbstractWe demonstrate through precise numerical simulations the possibility of flexible, thin-film solar cells, consisting of crystalline silicon, to achieve power conversion efficiency of 31%. Our optimized photonic crystal architecture consists of a 15 μm thick cell patterned with inverted micro-pyramids with lattice spacing comparable to the wavelength of near-infrared light, enabling strong wave-interference based light trapping and absorption. Unlike previous photonic crystal designs, photogenerated charge carrier flow is guided to a grid of interdigitated back contacts with optimized geometry to minimize Auger recombination losses due to lateral current flow. Front and back surface fields provided by optimized Gaussian doping profiles are shown to play a vital role in enhancing surface passivation. We carefully delineate the drop in power conversion efficiency when surface recombination velocities exceed 100 cm/s and the doping profiles deviate from prescribed values. These results are obtained by exact numerical simulation of Maxwell’s wave equations for light propagation throughout the cell architecture and a state-of-the-art model for charge carrier transport and Auger recombination.
Auditory and Cognitive Attributes of Hearing Aid Acclimatization in Individuals With Sensorineural Hearing Loss
Authors: Megha  , Maruthy Sandeep 
Published: August 2019

PurposeThe study aimed to investigate the underlying mechanisms of perceived benefit of hearing aid acclimatization. Specifically, measures in the auditory and cognitive domain were tapped to investigate its relationship with the perceived benefit.MethodTwenty-six individuals with sensorineural hearing loss served as participants for the study. The perceived benefit of hearing aid use was assessed using the Speech, Spatial and Qualities of Hearing Scale (SSQ;Gatehouse & Noble, 2004). Signal-to-noise ratio-50 (SNR-50) and acceptable noise levels were the measures in auditory domain, whereas working memory and listening effort (LE) were the measures in cognitive domain. All the measures were tracked over a span of 2 months of hearing aid use to determine the benefits of hearing aid acclimatization.ResultsThe SSQ showed improvements from baseline to 2nd month of hearing aid use. The mean improvement in the SNR-50 scores was 3.19 dB from the baseline. Acceptable noise levels and working memory did not change with hearing aid use. LE showed improvements in quiet but not in noise. The improvements in the SSQ were found to relate with the improvements in SNR-50.ConclusionsThe study indicated a significant perceived benefit with hearing aid acclimatization, and the underlying mechanism appears to be the signal-to-noise ratio gain. The findings of LE indicated reduced LE, thereby suggesting lesser cognitive load with hearing aid acclimatization. In addition, the individuals who performed poorer in the baseline measurement showed greater perceived benefit with hearing aid acclimatization.Supplemental Materialhttps://doi.org/10.23641/asha.9253175
A Novel Stimulation Paradigm for Obtaining Interfrequency Amplitude Ratio of Ocular Vestibular Evoked Myogenic Potentials
Authors: Singh Niraj Kumar , Kumar Prawin , Jha Raghav Hira 
Published: August 2019

Purpose
Interfrequency amplitude ratio (IFAR), the ratio of amplitude between ocular vestibular evoked myogenic potentials (oVEMPs) for tone bursts of 500 and 1000 Hz, aids in identification of Ménière's disease with high sensitivity and specificity. However, it requires recording of oVEMP for 2 frequencies, which doubles the time of recording. Use of simultaneous recording of responses for both frequencies could potentially bring down testing time. Simultaneous recording might be possible by modifying the oddball paradigm and using a ratio of 1:1 for the 2 frequencies. This might also reduce variation in oVEMP amplitude between frequencies due to changes in gaze angle between the recordings. However, it remains to be explored whether or not the use of modified oddball paradigm to record oVEMP (MoVEMP) will produce comparable responses to conventional sequential recording of oVEMP (CoVEMP) for obtaining IFAR. Hence, the study aimed to compare MoVEMP and CoVEMP on various measures of oVEMP.

Method
The study included 29 healthy adults in the age range of 18–30 years, 23 of which were used for validation and 6 for finding test–retest reliability. All participants underwent contralateral oVEMP recording using 500- and 1000-Hz tone bursts presented using MoVEMP and CoVEMP paradigms.

Results
Comparable outcomes on latencies, amplitude, and IFAR were obtained between CoVEMP and MoVEMP. Furthermore, MoVEMP took significantly lesser time per ear and also produced better test–retest reliability than CoVEMP.

Conclusion
MoVEMP is a quicker and more reliable clinical stimulation paradigm for obtaining IFAR than CoVEMP.
The Influence of Efferent Inhibition on Speech Perception in Noise: A Revisit Through Its Level-Dependent Function
Authors: Yashaswini L. , Maruthy Sandeep 
Published: August 2019

PurposeThe study aimed to assess the relationship between the level-dependent function of efferent inhibition and speech perception in noise across different intensities of suppressor and across different signal-to-noise ratios (SNRs) of speech.MethodTwenty-six young normal-hearing adults participated in the study. Contralateral suppression of transient evoked otoacoustic emissions (TEOAEs) was measured for 3 levels of suppressor (40, 50, and 60 dB SPL). Speech identification score (SIS) was measured at 5 ipsilateral SNR conditions (quiet, 0, −5, −10, and −15 dB), with and without contralateral broadband noise at 3 levels (40, 50, and 60 dB SPL). Furthermore, SNR-50 was measured with and without the same 3 levels of contralateral broadband noise.ResultsThe results showed that the suppression magnitude of TEOAE increased with an increase in suppressor level. However, neither SIS nor SNR-50 was influenced by the contralateral noise. In addition, SIS and SNR-50 did not show significant correlation with contralateral suppression of TEOAEs. This was true at all the SNRs and contralateral noise levels used in the study.ConclusionsThe findings suggest that the intensity of noise directly influences medial olivocochlear bundle–mediated efferent inhibition. However, the role of the medial olivocochlear bundle in regulating speech perception in noise needs to be revisited.Supplemental Materialhttps://doi.org/10.23641/asha.9336353
Radio loudness along the quasar main sequence
Authors: Ganci V. , Marziani P. , D’Onofrio M. , del Olmo A. , Bon E. , Bon N. , Negrete C. A. 
Published: August 2019

Context.When can an active galactic nucleus (AGN) be considered radio loud (RL)? Following the established view of the AGNs inner workings, an AGN is RL if associated with relativistic ejections emitting a radio synchrotron spectrum (i.e., it is a “jetted” AGN). In this paper we exploit the AGN main sequence that offers a powerful tool to contextualize radio properties.Aims.If large samples of optically-selected quasars are considered, AGNs are identified as RL if their Kellermann’s radio loudness ratioRK >  10. Our aims are to characterize the optical properties of different classes based on radio loudness within the main sequence and to test whether the conditionRK >  10 is sufficient for the identification of RL AGNs, since the origin of relatively strong radio emission may not be necessarily due to relativistic ejection.Methods.A sample of 355 quasars was selected by cross-correlating the Very Large Array Faint Images of the Radio Sky at Twenty-Centimeters survey (FIRST) with the twelfth release of the Sloan Digital Sky Survey Quasar Catalog published in 2017. We classified the optical spectra according to their spectral types along the main sequence of quasars. For each spectral type, we distinguished compact and extended morphology (providing a FIRST-based atlas of radio maps in the latter case), and three classes of radio loudness: detected ( specific flux ratio in thegband and at 1.4 GHz,R′K< 10), intermediate (10 ≤R′K< 70), and RL (R′K≥ 70).Results.The analysis revealed systematic differences between radio-detected (i.e., radio-quiet), radio-intermediate, and RL classes in each spectral type along the main sequence. We show that spectral bins that contain the extreme Population A sources have radio power compatible with emission by mechanisms ultimately due to star formation processes. RL sources of Population B are characteristically jetted. Their broad Hβprofiles can be interpreted as due to a binary broad-line region. We suggest that RL Population B sources should be preferential targets for the search of black hole binaries, and present a sample of binary black hole AGN candidates.Conclusions.The validity of the Kellermann’s criterion may be dependent on the source location along the quasar main sequence. The consideration of the main sequence trends allowed us to distinguish between sources whose radio emission mechanisms is jetted from the ones where the mechanism is likely to be fundamentally different.
A variational formulation for computing shape derivatives of geometric constraints along rays
Authors: Feppon Florian , Allaire Grégoire , Dapogny Charles 
Published: August 2019

In the formulation of shape optimization problems, multiple geometric constraint functionals involve the signed distance function to the optimized shape Ω. The numerical evaluation of their shape derivatives requires to integrate some quantities along the normal rays to Ω, a challenging operation to implement, which is usually achieved thanks to the method of characteristics. The goal of the present paper is to propose an alternative, variational approach for this purpose. Our method amounts, in full generality, to compute integral quantities along the characteristic curves of a given velocity field without requiring the explicit knowledge of these curves on the spatial discretization; it rather relies on a variational problem which can be solved conveniently by the finite element method. The well-posedness of this problem is established thanks to a detailed analysis of weighted graph spaces of the advection operator β ⋅ ∇ associated to a C1 velocity field β. One novelty of our approach is the ability to handle velocity fields with possibly unbounded divergence: we do not assume div(β) ∈ L∞. Our working assumptions are fulfilled in the context of shape optimization of C2 domains Ω, where the velocity field β = ∇dΩ is an extension of the unit outward normal vector to the optimized shape. The efficiency of our variational method with respect to the direct integration of numerical quantities along rays is evaluated on several numerical examples. Classical albeit important implementation issues such as the calculation of a shape’s curvature and the detection of its skeleton are discussed. Finally, we demonstrate the convenience and potential of our method when it comes to enforcing maximum and minimum thickness constraints in structural shape optimization.
Antibacterial and Remineralization Efficacy of Casein Phosphopeptide, Glycomacropeptide Nanocomplex, and Probiotics in Experimental Toothpastes: An In Vitro Comparative Study
Authors: Elgamily Hanaa , Safwat Engie , Soliman Zainab , Salama Heba , El-Sayed Hoda , Anwar Mohamed 
Published: August 2019

Abstract
Objective This article evaluates the antibacterial and remineralization potential of experimentally prepared toothpastes containing different mixtures of nano casein phosphopeptides (nCPP), nano amorphous calcium phosphate (nACP), probiotic ­ Lactobacillus rhamnosus B-445 (L. rhamnosus), and nano glycomacropeptide (nGMP).
Materials and Methods Five experimental toothpaste samples were prepared and grouped, such that group (A0) was the experimental toothpaste base formula. Groups (A1), (A2), (A3), and (A4) were the experimental toothpastes containing: nCPP; nCPP and nACP; nCPP, nACP, and L. rhamnosus, and nCPP, nACP, and nGMP, ­respectively. Group (A5) was the commercial group (GC MI Paste Plus). The five groups were screened against Streptococcus mutans (ATCC 25175) growth, and investigated for their remineralizing potentials on demineralized bovine enamel using Vickers ­microhardness test (Vickers hardness number [VHN]). Scanning electron microscope (SEM) images were obtained for the demineralized and remineralized enamel of the two most effective toothpastes against in vitro bacterial induced enamel demineralization. Statistical analysis was performed using one-way analysis of variance (ANOVA) as well as repeated measures ANOVA followed by Tukey’s post hoc test.
Results Both (A3) and (A4) were significantly higher in mean inhibition zone ­diameters than group (A1) and (A2). Group (A4) showed the highest statistical ­significance in the mean difference between VHN values of demineralization and 15 days remineralization period. SEM images showed the deposition of nano-sized particles fill the ­microrough surface pattern of the etched enamel.
Conclusion All these findings suggest the use of probiotic, nCPP–nACP, and nGMP as a dental anticariogenic and remineralizing active agents.
Nurses' Expectations of an Inpatient Portal for Hospitalized Patients and Caregivers
Authors: Hoonakker Peter L. T. , Rankin Rebecca J. , Passini Jennifer C. , Bunton Jenny A. , Ehlenfeldt Bradley D. , Dean Shannon M. , Thurber Anne S. , Kelly Michelle M. 
Published: August 2019

Background Patient portals are intended to engage patients and enhance patient-centered care. Recent studies suggest that the information within portals could provide benefits to patients and their caregivers during hospitalization; however, few studies have examined nurse and staff expectations of portals when used in the hospital setting.
Objective This article examines inpatient nurse and support staff expectations of a commercially available inpatient portal prior to its hospital-wide implementation.
Methods In this cross-sectional study, nurses and support staff were surveyed 1 month prior to the implementation of an inpatient portal for patients. Items included respondent characteristics, satisfaction with online inpatient portal training, expectations of the effects of portal use on patients, caregivers, and staff, overall acceptance, and barriers to its implementation.
Results Of 881 respondents, 73.0% were staff nurses, 18.4% nurse assistants, 4.3% unit coordinators, and 1.2% nurse managers. Respondents were generally satisfied with the portal information they received from online training. A majority liked the portal to some extent prior to its use (66.7%); however, they noted multiple implementation barriers, including: tablets would get lost/damaged (66.2% of respondents), patients and/or caregivers would have too many questions (48.5%), and staff would have problems integrating it into their workflow (44.7%). Respondents working on medical units had higher expectations (p < 0.001) and acceptance (p < 0.01) of the portal than those on surgical and intensive care units. Nurse managers were more positive than respondents with other job roles were (all p < 0.001).
Conclusion Overall, nurse and support staff had high expectations of the effects of inpatient portal use prior to its hospital-wide implementation. They thought it would benefit patients and/or their caregivers; however, they also perceived several barriers to its implementation. These results will be used in conjunction with patient and caregiver perspectives to inform future efforts to evaluate and improve upon inpatient portal implementation and dissemination across health systems.