bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilization of Nerve Integrity Monitor for Promontory Stimulation Testing Prior to Cochlear Implant
Authors: Kelly Elizabeth A. , Levine Samuel , Gravel Kristin E. , Hart Dianna L. , Huang Tina 
Published: January 2018

Objective:
To demonstrate the feasibility of a nerve integrity monitor as a tool for promontory stimulation testing in patients with profound sensorineural hearing loss considering cochlear implantation.

Patients:
Adult patients considered for cochlear implantation with no auditory response on audiometric testing

Intervention:
Promontory stimulation testing using the nerve integrity monitor.

Main Outcome Measure:
By using a facial nerve stimulator and the nerve integrity monitor, transtympanic promontory stimulation testing was performed to assess auditory nerve function and determine candidacy for cochlear implantation. Patients indicated if they heard the stimulus.

Results:
Of the four patients completing the promontory stimulation tests, three patients heard the stimulus and one patient did not hear the stimulus. Of the three patients with a positive stimulation test, two patients have a history of progressive profound sensorineural hearing loss and one patient had a history of severe blunt temporal bone trauma. Two of these patients proceeded with cochlear implantation. The patient who had a negative promontory stimulation test has a history of neurofibromatosis type 2.

Conclusion:
The nerve integrity monitor is a convenient tool that can be used in the clinic setting to perform promontory stimulation tests and aid in determining cochlear implant candidates, specifically in those patients who require verification of auditory nerve function. This tool is a feasible and reasonable method for promontory stimulation testing.
Audiological Outcomes in Growing Vestibular Schwannomas Managed Either Conservatively, or With Stereotactic Radiosurgery
Authors: Milner Thomas Daniel , Locke Richard R. , Kontorinis Georgios , Crowther John A. 
Published: January 2018

Objective:
Recent studies have suggested good hearing preservation following stereotactic radiosurgery (STRS) in patients with vestibular schwannomas (VS). This study aims to assess audiological outcomes in patients with growing VS treated either with STRS, or managed conservatively.

Study Design:
Retrospective cohort study.

Setting:
Tertiary referral center.

Patients:
Out of 540 patients with VS, 69 patients with growing VS fulfilled the inclusion criteria; 24 treated conservatively and 45 with STRS. VS were considered growing if demonstrating more than 15% tumor volume increase during 1 year of watchful waiting.

Intervention:
American Association of Otolaryngology–Head and Neck Surgery (AAOHNS) hearing threshold (dB averaged over 500–3000 Hz) deterioration and Gardner–Robertson class deterioration over time were used as the primary outcome measures. Rate of progression to loss of functional hearing (Gardner–Robertson class I–II) was also determined between cohorts.

Results:
Mean follow-up was similar between treatment cohorts (STRS = 69.6 mo, conservative management = 71.7 mo). There was no significant difference in AAOHNS deterioration (t = 1.05, df = 53, p = 0.301) or Gardner–Robertson deterioration (χ
2 = 0.47, df = 1, p = 0.492) between cohorts. Furthermore, rate of progression to loss of functional hearing was similar between cohorts (Hazard ratio = 0.704, 95% CI 0.287–1.728, p = 0.44). In STRS patients, AAOHNS deterioration was greater in those with lower AAOHNS thresholds at diagnosis (t = –2.683, df = 28, p = 0.0121). Similarly, Gardner–Robertson deterioration was significantly more likely in STRS patients with functional hearing (Gardner–Robertson class I–II) (Adjusted odds ratio = 32.14, 95% CI 3.15–328, p = 0.0034).

Conclusions:
STRS results in similar audiological outcomes compared with patients managed conservatively; Consequently, STRS given to patients with VS to preserve hearing is not justified. In contrast to recent studies, patients with preserved hearing at diagnosis have significantly greater audiological deterioration when undergoing STRS.
Long-Term Hearing Preservation Outcomes for Small Vestibular Schwannomas: Retrosigmoid Removal Versus Observation
Authors: Zhu Weidong , Chen Hongsai , Jia Huan , Chai Yongchuan , Yang Jie , Wang Zhaoyan , Wu Hao 
Published: January 2018

Objective:
Management of small vestibular schwannomas (VSs) consists of three options: serial observation, radiosurgery, and microsurgery. The authors reported the long-term hearing outcomes after retrosigmoid tumor removal in 110 patients and hearing follow-up outcomes in 160 serial observation patients with small VSs to explore the appropriate management strategy and predictive factors of hearing preservation for small VSs.

Study Design:
Retrospective study.

Setting:
Tertiary referral center.

Patients:
In this study, 110 patients with small VS (purely intracanalicular/cerebellopontine angle tumor ≤15 mm) during a 15-year period, from January 2001 to December 2015, were candidates for hearing preservation surgery through retrosigmoid approach, while 160 patients were candidates for serial observation. The main outcome measure was preservation of hearing under different hearing levels, assessed with the classification of American Academy of Otolaryngology–Head and Neck Surgery.

Results:
Preoperative hearing levels of the 110 study patients were Class A in 49 patients, Class B in 43 patients, and Class C in 18 patients. In all surgery patients (n = 110), 97.3% (107/110) patients maintained the same level during postoperative follow-up (mean follow-up time was 49.1 ± 28.2 mo) and 86 (78.2%) had complete radiologic and audiometric data at least 4 years follow-up for review. In the 4 years follow-up surgery group (n = 86), postoperative hearing levels were Class A, B, C, and D for 22, 11, 18, and 35 patients, and postoperative rates of preservation of serviceable and useful hearing were 59.3% (51/86) and 47.1% (33/70), respectively. In serial observation group, mean follow-up time was 35.2 ± 33.1 months; mean tumor size at presentation was 8.6 ± 4.3 mm; overall mean tumor growth rate was 1.08 ± 2.3 mm/yr; serviceable hearing preservation rate of 98 patients was 54.1% (53/98) at the 5-year end point and 48.7% (37/76) at the 7-year end point.

Conclusion:
Tumor removal should be the first treatment option for patients with small VSs and preserved hearing, especially for young patients with good hearing; retrosigmoid approach is an effective and safe approach for small VSs removal with excellent functional outcomes; better preoperative hearing predicted a higher rate of postoperative hearing preservation; patients without fundal extension were more likely to achieve hearing preservation than those with fundal extension, but no difference had been detected when retrosigmoid removal assisted with endoscope was performed; patients with small tumors originating from SVN were more likely to achieve hearing preservation compared with those with IVN-originating tumors.
Vestibular Function and Gross Motor Development in 195 Children With Congenital Hearing Loss—Assessment of Inner Ear Malformations
Authors: Kimura Yusuke , Masuda Takeshi , Kaga Kimitaka 
Published: January 2018

Objectives:
To evaluate the relationship between vestibular function and gross motor development in children with inner ear malformations.

Methods:
A total of 195 children (average age: 2.4 ± 1.6 yr) with profound hearing loss, defined as a hearing threshold greater than 80 dB, participated in this study. Evaluation of vestibular function was assessed in all children using a damped rotational chair test. Gross motor development was assessed by examining the age of acquisition of head control and independent walking. Temporal bone computed tomography scans were conducted in 190 of the 195 children.

Results:
Among the 195 children, 31 children (15.9%) showed a reduced response in the rotational chair test. Of the 17 children who were followed up with repeat rotational chair tests, 16 showed more obvious nystagmus during follow-up compared with the initial examination. The reduced response group showed significant delays in head control and independent walking compared with the normal response group (p < 0.01). Forty-one children (21.6%) demonstrated inner ear malformations and showed significantly delayed acquisition of head control and independent walking (p < 0.01) compared with children with normal vestibular function. Children with inner ear malformations with a reduced response in the rotational chair test had severe vestibular (p < 0.05) and lateral semicircular canal (p < 0.01) malformations as the most common findings.

Conclusions:
Structural inner ear malformations are associated with vestibular dysfunction and delayed gross motor development. Our findings confirm that there is a higher incidence of reduced vestibulo-ocular reflex in children with vestibular and semicircular canal malformations.
Characteristics and comorbidities of inpatients without celiac disease on a gluten-free diet
Authors: Blackett John W. , Shamsunder Meghana , Reilly Norelle R. , Green Peter H.R. , Lebwohl Benjamin 
Published: January 2018

Objectives
Despite the increasing popularity of gluten-free diet (GFD), the demographic characteristics and medical features of patients without celiac disease on this diet have not been extensively investigated.
We aimed to characterize the medical conditions and demographic backgrounds of hospitalized patients without celiac disease who adhere to a GFD, to further understand their reasons for gluten avoidance.

Materials and methods
We performed an observational cohort study on all inpatients at Columbia University Medical Center on a GFD in 2011–2016, excluding those with celiac disease, compared with age-matched and sex-matched inpatients on a regular diet. We determined the odds ratio (OR) of being on a GFD for various comorbidities using conditional logistic regression.

Results
Of 769 inpatients on a GFD, most (63.6%) did not have celiac disease. Gluten-avoiding patients were more likely to be non-Hispanic Whites [OR: 2.92; 95% confidence interval (CI): 2.31–3.70]. They had a lower prevalence of hypertension (OR: 0.38; 95% CI: 0.27–0.52) and diabetes (OR: 0.58; 95% CI: 0.32–0.75) and higher prevalence of inflammatory bowel disease (OR: 1.56; 95% CI: 1.02–2.41), irritable bowel syndrome (OR: 6.16; 95% CI: 2.11–10.23), hyperthyroidism (OR: 2.73; 95% CI: 1.22–6.10), hypothyroidism (OR: 2.06; 95% CI: 1.39–3.06), lupus (OR: 2.87; 95% CI: 1.13–7.29), and autism spectrum disorder (OR: 23.42; 95% CI: 5.29–103.73).

Conclusion
Nonceliac gluten-avoiding patients have higher prevalences of inflammatory bowel disease, irritable bowel syndrome, thyroid disease, lupus, and autism spectrum disorder, suggesting patients with these disorders have turned to a GFD for perceived benefit, despite a scant evidence basis.
Thermoelectric magnetohydrodynamic effects on the crystal growth rate of undercooled Ni dendrites
Authors: Kao A. , Gao J. , Pericleous K. 
Published: January 2018

In the undercooled solidification of pure metals, the dendrite tip velocity has been shown experimentally to have a strong dependence on the intensity of an external magnetic field, exhibiting several maxima and minima. In the experiments conducted in China, the undercooled solidification dynamics of pure Ni was studied using the glass fluxing method. Visual recordings of the progress of solidification are compared at different static fields up to 6 T. The introduction of microscopic convective transport through thermoelectric magnetohydrodynamics is a promising explanation for the observed changes of tip velocities. To address this problem, a purpose-built numerical code was used to solve the coupled equations representing the magnetohydrodynamic, thermal and solidification mechanisms. The underlying phenomena can be attributed to two competing flow fields, which were generated by orthogonal components of the magnetic field, parallel and transverse to the direction of growth. Their effects are either intensified or damped out with increasing magnetic field intensity, leading to the observed behaviour of the tip velocity. The results obtained reflect well the experimental findings.
This article is part of the theme issue ‘From atomistic interfaces to dendritic patterns’.
Nonlinear dynamics of mushy layers induced by external stochastic fluctuations
Authors: Alexandrov Dmitri V. , Bashkirtseva Irina A. , Ryashko Lev B. 
Published: January 2018

The time-dependent process of directional crystallization in the presence of a mushy layer is considered with allowance for arbitrary fluctuations in the atmospheric temperature and friction velocity. A nonlinear set of mushy layer equations and boundary conditions is solved analytically when the heat and mass fluxes at the boundary between the mushy layer and liquid phase are induced by turbulent motion in the liquid and, as a result, have the corresponding convective form. Namely, the ‘solid phase–mushy layer’ and ‘mushy layer–liquid phase’ phase transition boundaries as well as the solid fraction, temperature and concentration (salinity) distributions are found. If the atmospheric temperature and friction velocity are constant, the analytical solution takes a parametric form. In the more common case when they represent arbitrary functions of time, the analytical solution is given by means of the standard Cauchy problem. The deterministic and stochastic behaviour of the phase transition process is analysed on the basis of the obtained analytical solutions. In the case of stochastic fluctuations in the atmospheric temperature and friction velocity, the phase transition interfaces (mushy layer boundaries) move faster than in the deterministic case. A cumulative effect of these noise contributions is revealed as well. In other words, when the atmospheric temperature and friction velocity fluctuate simultaneously due to the influence of different external processes and phenomena, the phase transition boundaries move even faster. This article is part of the theme issue ‘From atomistic interfaces to dendritic patterns’.
This article is part of the theme issue ‘From atomistic interfaces to dendritic patterns’.
Expression variation and covariation impair analog and enable binary signaling control
Authors: Kovary Kyle M. , Taylor Brooks , Zhao Michael L. , Teruel Mary N. 
Published: January 2018

AbstractDue to noise in the synthesis and degradation of proteins, the concentrations of individual vertebrate signaling proteins were estimated to vary with a coefficient of variation (CV) of approximately 25% between cells. This high variation enables population-level regulation of cell functions but abolishes accurate single-cell signal transmission. Here we measure cell-to-cell variability of relative protein abundance using quantitative proteomics of individual Xenopus laevis eggs and cultured human cells and show that variation is typically much lower, in the range of 5–15%, compatible with accurate single-cell transmission. Furthermore, we show that MEK and ERK expression covary which improves controllability of the fraction of cells that activate bimodal ERK signaling, arguing that covariation has a role in facilitating population-level control of binary cell-fate decisions. Together, our experimental and model data argues for a control principle whereby low covariation limits signaling noise for accurate control analog single-cell signaling. In contrast, increased covariation widens the stimulus-range over which external inputs can regulate binary cell activation, thereby enabling accurate control of the fraction of activated cells at the population level.
Functional mapping of the mousehairlessgene promoter region
Authors: Folco Eric G. , Nonchev Stefan 
Published: January 2018

AbstractThe mousehairlessgene (Hr) encodes a protein of 127 kDa, acting as corepressor of nuclear hormone receptors. The Hairless protein (HR) is involved in the control of the cellular transition to the first hair cycle in adult Mammals. In its absence hair follicles disintegrate leading to a complete and irreversible hair loss with formation of cutaneous cysts. The hairless phenotype is therefore linked to defective proliferation and migration of the hair follicle stem cells apparently unable to respond to various signalling molecules. TheHrgene is expressed at high levels in skin and brain, andhairlesstranscripts were detected in gonads, thymus and colon. Although the patterns ofHrexpression appear to be spatially and temporally regulated, very little is known about the molecular basis of the transcriptional control underlyingHrgene function. In this work we determine the precise transcriptional initiation start site of the mouseHrgene and identify a new 1,1 kb cis-control element (RE1) that encompasses the promoter region and is able to drive luciferase reporter expression in skin and brain derived cell lines. We performed a deletion analysis and explored functionally regulatory motifs within this fragment to show that the role of this upstream regulatory region is linked to the presence of TRE and VDRE binding sites. We find that a TRE situated at –300 bp from the cap site is essential for gene expression in both skin NIH 3T3 and GHFT1 cells, while a VDRE positioned 94 bp upstream of the TRE modulates reporter expression specifically in skin derived cell lines. In addition, we define a novel cis-regulatory motif UE60, situated at the 5’-end of RE1 and likely to interact with both TRE and VDRE. Our data complete previous results on the possible existence of an autoregulatory pathway, implicated inHrgene regulation. Taken together these findings reveal a complex molecular network that potentially links several signalling pathways in hair follicle formation. We discuss the organisation of the regulatory modules in the mouseHrgene upstream DNA sequences in the light of the high homology of this region in mouse, rat and human.
HOTAIRprimes the Ewing sarcoma family of tumors for tumorigenesis via epigenetic dysregulation involving LSD1
Authors: Siddiqui Hasan , Selich-Anderson Julia , Felgenhauer Joshua , Fitch James , Nadella Vijay , Taslim Cenny , Tomino Laura , Theisen Emily , Otsuru Satoru , Horwitz Edwin , Lessnick Stephen , White Peter , Shah Nilay 
Published: January 2018

AbstractThe EWS-FLI1 fusion protein drives oncogenesis in the Ewing sarcoma family of tumors (ESFT) in humans, but its toxicity in normal cells requires additional cellular events for oncogenesis. We show that the lncRNAHOTAIRmaintains cell viability in the presence of EWS-FLI1 and redirects epigenetic regulation in ESFT.HOTAIRis consistently overexpressed in ESFTs and is not driven by EWS-FLI1. Repression ofHOTAIRin ESFT cell lines significantly reduces anchorage-independent colony formation in vitro and impairs tumor xenograft growth in vivo. Overexpression ofHOTAIRin human mesenchymal stem cells (hMSCs), a putative cell of origin of ESFT, and IMR90 cells induces colony formation. Critically, HOTAIR-expressing hMSCs and IMR90 cells remain viable with subsequentEWS-FLI1expression.HOTAIRinduces histone modifications and gene repression through interaction with the epigenetic modifier LSD1 in ESFT cell lines and hTERT-hMSCs. Our findings suggest thatHOTAIRmaintains ESFT viability through epigenetic dysregulation.SignificanceWhile theEWS-FLI1fusion gene was determined to be the oncogenic driver in the overwhelming majority of ESFT, it is toxic to cell physiology and requires one or more additional molecular events to maintain cell viability. As these tumors have surprisingly few genetic mutations at diagnosis, epigenetic changes have been considered to be such an event, but the mechanism by which these changes are driven remains unclear. Our work shows thatHOTAIRis consistently expressed among ESFT and induces epigenetic and gene expression changes that cooperate in tumorigenesis. Furthermore, expression ofHOTAIRallows for cell viability in the setting of subsequentEWS-FLI1expression. Our findings elucidate new steps of malignant transformation in this cancer and identify novel therapeutic targets.
A metal-dependent switch moderates activity of the hexameric M17 aminopeptidases
Authors: Drinkwater Nyssa , Yang Wei , Riley Blake T. , Hayes Brooke K. , Sivaraman Komagal Kannan , Malcolm Tess R. , Atkinson Sarah C. , Borg Natalie A. , Kass Itamar , Buckle Ashley M. , McGowan Sheena 
Published: January 2018

AbstractThe metal-dependent M17 aminopeptidases are conserved throughout all kingdoms of life. The large enzyme family is characterised by a conserved binuclear metal center and a distinctive homohexameric arrangement. To understand the mechanistic role of the hexameric assembly, we undertook an investigation of the structure and dynamics of the M17 aminopeptidase fromP. falciparum,PfA-M17. We describe a novel structure ofPfA-M17, which shows that the active sites of each trimer are linked by a dynamic loop, and that the loop movement is coupled with a drastic rearrangement of the binuclear metal center and substrate-binding pocket. Molecular dynamics simulations, supported by biochemical analyses ofPfA-M17 variants, demonstrate that this rearrangement is inherent toPfA-M17, and that the transition between the active and inactive states is part of a dynamic regulatory mechanism. Key to the mechanism is a re-modelling of the binuclear metal center, which occurs in response to a signal from the neighbouring active site, and serves to moderate the rate of proteolysis under different environmental conditions. Therefore, this work has identified the precise mechanism by which oligomerization contributes toPfA-M17 function. Further, it has described a novel role for metal cofactors in the regulation of enzymes with implications for the wide range of metalloenzymes that operate via a two-metal ion catalytic center including DNA processing enzymes and metalloproteases.
Comparative genomics ofPseudomonas syringaereveals convergent gene gain and loss associated with specialisation onto cherry (Prunus avium)
Authors: Hulin Michelle T. , Armitage Andrew D. , Vicente Joana G. , Holub Eric B. , Baxter Laura , Bates Helen J. , Mansfield John W. , Jackson Robert W. , Harrison Richard J. 
Published: January 2018

SummaryGenome-wide analyses of the effector- and toxin-encoding genes were used to examine the phylogenetics and evolution of pathogenicity amongst diverse strains ofPseudomonas syringaecausing bacterial canker of cherry (Prunus avium) including pathovarsP.spv.morsprunorum(Psm) races 1 and 2,P.spv.syringae(Pss) andP.spv.avii.Genome-based phylogenetic analyses revealedPsmraces andP.spv.aviiclades were distinct and were each monophyletic, whereas cherry-pathogenic strains ofPsswere interspersed amongst strains from other host species.A maximum likelihood approach was used to predict effectors associated with host specialisation on cherry.Psspossesses a smaller repertoire of type III effectors but has more toxin biosynthesis clusters compared withPsmandP.spv.avii. Evolution of cherry pathogenicity was correlated with gain of genes such ashopAR1andhopBB1through putative phage transfer and horizontal transfer, respectively. By contrast, loss of theavrPto/hopABredundant effector group was observed in cherry-pathogenic clades. Ectopic expression ofhopABandhopC1triggered the hypersensitive reaction in cherry leaves, confirming computational predictions.Cherry canker provides a fascinating example of convergent evolution of pathogenicity that is explained by the mix of effector and toxin repertoires acting on a common host.