bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preservation of Cells of the Organ of Corti and Innervating Dendritic Processes Following Cochlear Implantation in the Human: An Immunohistochemical Study
Authors: Kamakura Takefumi , O’Malley Jennifer T. , Nadol Joseph B. 
Published: January 2018

Hypothesis:
This study evaluates the degree of preservation of hair cells, supporting cells, and innervating dendritic processes after cochlear implantation in the human using immunohistochemical methods.

Background:
Surgical insertion of a cochlear implant electrode induces various pathologic changes within the cochlea including insertional trauma, foreign body response, inflammation, fibrosis, and neo-osteogenesis. These changes may result in loss of residual acoustic hearing, adversely affecting the use of hybrid implants, and may result in loss of putative precursor cells, limiting the success of future regenerative protocols.

Methods:
Twenty-eight celloidin-embedded temporal bones from 14 patients with bilateral severe to profound sensorineural hearing loss and unilateral cochlear implants were studied. Two sections including the modiolus or basal turn from each temporal bone were stained using antineurofilament, antimyosin-VIIa, and antitubulin antibodies in both the implanted and unimplanted ears.

Results:
Inner and outer hair cells: Immunoreactivity was reduced throughout the implanted cochlea and in the unimplanted cochlea with the exception of the apical turn.
Dendritic processes in the osseous spiral lamina: Immunoreactivity was significantly less along the electrode of the implanted cochlea than in the other segments.
Inner and outer pillars, inner and outer spiral bundles, and Deiters’ cells: Immunoreactivity was similar in the implanted and unimplanted cochleae.

Conclusion:
Insertion of a cochlear implant electrode may significantly affect the inner and outer hair cells both along and apical to the electrode, and dendritic processes in the osseous spiral lamina along the electrode. There was less effect on pillar cells, Deiters’ cells, and spiral bundles.
Audiologic Natural History of Small Volume Cochleovestibular Schwannomas in Neurofibromatosis Type 2
Authors: deTorres Alvin T. , Brewer Carmen C. , Zalewski Chris K. , King Kelly A. , Walker Robert , Scott Gretchen C. , Asthagiri Ashok R. , Chittiboina Prashant , Kim Hung Jeffrey 
Published: January 2018

Objective:
To characterize the audiometric natural progression in patient-ears with small volume (<1,000 mm3), treatment-naïve cochleovestibular schwannomas (CVSs) in Neurofibromatosis Type 2 (NF2).

Study Design:
Prospective, longitudinal cohort study.

Setting:
Quaternary medical research institute.

Patients:
One hundred eleven ears in 71 NF2 patients with small, treatment-naïve CVSs observed from July 2006 to July 2016.

Intervention:
Serial audiometric testing, including pure tone audiometry, speech audiometry, and magnetic resonance imaging (MRI).

Outcome Measures:
Four-frequency pure tone average (4f-PTA) of 0.5, 1, 2, and 4 kHz and word recognition score (WRS) were recorded. Their changes were compared with MRI changes in CVS volume over time. Times to significant hearing loss (10 dB loss in 4f-PTA) and WRS based on 95% critical difference were measured.

Results:
Linear regression analysis showed a significant correlation with baseline hearing level (4f-PTA) and internal auditory canal (IAC) tumor volume to annual hearing decrease rate (AHDR) (p = 0.003, p = 0.0004). Hearing level at baseline and tumor volume correlate with AHDR while tumor volume growth rate does not. Two-way analysis of variance found significant differences in AHDR, risk of significant hearing loss, and risk of critical difference in WRS based on baseline hearing level (abnormal or normal) and IAC tumor volume (greater or less than 200 mm3).

Conclusion:
Subjects with normal baseline hearing and small IAC tumor component had a low AHDR and low risk of significant hearing loss and may warrant conservative management while the presence of baseline hearing loss and large IAC volume resulted in higher ADHR and greater risk for further hearing loss and may benefit from early treatment interventions.
The Impact of the Transcanal Endoscopic Approach and Mastoid Preservation on Recurrence of Primary Acquired Attic Cholesteatoma
Authors: Presutti Livio , Anschuetz Lukas , Rubini Alessia , Ruberto Marco , Alicandri-Ciufelli Matteo , Dematte Marco , Caversaccio Marco , Marchioni Daniele 
Published: January 2018

Objective:
We aim to investigate the factors associated with recurrent disease following surgery for primary acquired attic cholesteatoma. We hypothesize that minimal invasive, mucosal sparing operation techniques have beneficial effects on the outcome in terms of recurrence.

Study Design:
Retrospective study.

Setting:
Tertiary referral center.

Participants:
A total of 110 patients presenting with primary acquired attic cholesteatoma were enrolled in the study. Patients undergoing revision surgery or a canal wall down procedure, as well as patients with residual disease were excluded from the study.

Main Outcome Measures:
During follow-up recurrence was assessed and classified into normal, self-cleaning retraction pockets, or recurrent cholesteatoma requiring revision surgery.

Results:
We observed during follow-up statistically significant decrease (p = 0.036) in the occurrence of retraction pockets and recurrence in patients operated by the transcanal endoscopic approach (n = 55, 11% re-retraction, 9% recurrence) compared with those who underwent a canal wall up procedure (n = 55, 16% re-retraction, 22% recurrence). However, the multivariate model did not demonstrate statistically significant predictors regarding the outcome. Moreover, the preservation or direct reconstruction of the ossicular chain had a beneficial effect on the outcome. We observed 11% re-retraction and 9% recurrence in cases with preserved or reconstructed ossicular chain versus 18% re-retraction and 24% recurrence (p = 0.011) in cases of nonpreserved or non-reconstructed ossicular chain. A score was established according to the intraoperative mucosal damage and correlated to the occurrence of recurrence (p = 0.02). The risk of recurrence increased by 23.6% (95% confidence interval: 3.22–48.1) with each additional mucosal damage site.

Conclusion:
Transcanal endoscopic approaches that preserve the mastoid may play an important role in preventing recurrence and underscores the importance of the mucosa and mastoid air cells on middle ear homeostasis.
Neonatal hypoglycemia: continuous glucose monitoring
Authors: Shah Rajesh , McKinlay Christopher J.D. , Harding Jane E. 
Published: January 2018

Purpose of review
Continuous glucose monitoring (CGM) is increasingly used in the management of diabetes in children and adults, but there are few data regarding its use in neonates. The purpose of this article is to discuss the potential benefits and limitations of CGM in neonates.

Recent findings
Smaller electrodes in new sensors and real-time monitoring have made CGM devices more approachable for neonatal care. CGM is well tolerated in infants including very low birth weight babies, and few if any local complications have been reported. Use of CGM in newborns may reduce the frequency of blood sampling and improve glycemic stability, with more time spent in the euglycemic range. However, CGM may also lead to more intervention, with potential adverse effects on outcomes. More information is also needed about reliability, calibration and interpretation of CGM in the neonate.

Summary
Although the use of CGM in neonates appears to be well tolerated, feasible and has been associated with better glycemic status, there is not yet any evidence of improved clinical outcomes. Clinical utility of CGM should be demonstrated in randomized trials prior to its introduction into regular neonatal care.
Long-Term Impacts Faced by Patients and Families After Harmful Healthcare Events
Authors: Ottosen Madelene J. , Sedlock Emily W. , Aigbe Aitebureme O. , Bell Sigall K. , Gallagher Thomas H. , Thomas Eric J. 
Published: January 2018

Background
Patients and families report experiencing a multitude of harms from medical errors resulting in physical, emotional, and financial hardships. Little is known about the duration and nature of these harms and the type of support needed to promote patient and family healing after such events. We sought to describe the long-term impacts (LTIs) reported by patients and family members who experienced harmful medical events 5 or more years ago.

Methods
We performed a content analysis on 32 interviews originally conducted with 72 patients or family members about their views of the factors contributing to their self-reported harmful event. Interviews selected occurred 5 or more years after the harmful event and were grouped by time since event, 5 to 9 years (22 interviews) or 10 or more years (10 interviews) for analysis. We analyzed these interviews targeting spontaneous references of ongoing impacts experienced by the participants.

Results
Participants collectively described the following four LTIs: psychological, social/behavioral, physical, and financial. Most cited psychological impacts with half-reporting ongoing anger and vivid memories. More than half reported ongoing physical impacts and one-third experienced ongoing financial impacts. Long-term social and behavioral impacts such as alterations in lifestyle, self-identity, and healthcare seeking behaviors were the most highly reported.

Conclusions
These patients and families experienced many profound LTIs after their harmful medical event. For some, these impacts evolved into secondary harms ongoing 10 years and more after the event. Our results draw attention to the persistent impacts patients and families may experience long after harmful events and the need for future research to understand and support affected patients and families.
Brief Report: Racial Comparison of D-Dimer Levels in US Male Military Personnel Before and After HIV Infection and Viral Suppression
Authors: O'Bryan Thomas A. , Agan Brian K. , Tracy Russell P. , Freiberg Matthew S. , Okulicz Jason F. , So-Armah Kaku , Ganesan Anuradha , Rimland David , Lalani Tahaniyat , Deiss Robert G. , Tramont Edmund C. 
Published: January 2018

Background:
D-dimer blood levels in persons with HIV infection are associated with risk of serious non-AIDS conditions and death. Black race has been correlated with higher D-dimer levels in several studies. We examined the effects of race and HIV on D-dimer over time and the impact of viral load suppression by longitudinally comparing changes in levels among healthy young adult male African Americans and whites before HIV seroconversion and before and after initiation of antiretroviral therapy (ART).

Methods:
We analyzed D-dimer levels and clinical and laboratory data of 192 participants enrolled in the US Military HIV Natural History Study, a 30-year cohort of military personnel infected with HIV. D-dimer levels were measured on stored sera from each participant at 3 time points: (1) before HIV seroconversion (Pre-SC), (2) ≥6 months after HIV seroconversion but before ART initiation (Post-SC), and (3) ≥6 months after ART with documented viral suppression (Post-ART). Levels were compared at each time point using nonparametric and logistic regression analysis.

Results:
Compared with whites (n = 106), African Americans (n = 86) had higher D-dimer levels post-SC (P = 0.007), but in the same individuals, pre-SC baseline and post-ART levels were similar (P = 0.40 and P = 0.99, respectively). There were no racial differences in CD4 cell counts, HIV RNA viral load, time from estimated seroconversion to ART initiation, and duration on ART.

Conclusions:
Observed longitudinally, racial differences in D-dimer levels were seen only during HIV viremia. Higher levels of D-dimer commonly observed in African Americans are likely due to factors in addition to race.
Molecular parallelism in fast-twitch muscle proteins in echolocating mammals
Authors: Lee Jun-Hoe , Lewis Kevin M , Moural Timothy W , Kirilenko Bogdan , Borgonovo Barbara , Prange Gisa , Koessl Manfred , Huggenberger Stefan , Kang ChulHee , Hiller Michael 
Published: January 2018

AbstractDetecting associations between genomic changes and phenotypic differences is fundamental to understanding how phenotypes evolved. By systematically screening for parallel amino acid substitutions, we detected known as well as novel cases (Strc, Tecta, Cabp2) of parallelism between echolocating bats and toothed whales in proteins that could contribute to high frequency hearing adaptations. Interestingly, our screen also showed that echolocating mammals exhibit an unusually high number of parallel substitutions in fast-twitch muscle fiber proteins. Both bats and dolphins produce an extremely rapid call rate when homing in on their prey, which was shown in bats to be powered by specialized superfast muscles. We show that these genes with parallel substitutions (Casq1, Atp2a1, Myh2, Myl1) are expressed in the superfast sound-producing muscle of bats. Furthermore, we found that the calcium storage protein calsequestrin 1 of bats and dolphins functionally converged in its ability to form calcium-sequestering polymers at lower calcium concentrations, which may contribute to rapid calcium transients required for superfast muscle physiology. The proteins that our genomic screen detected could be involved in the convergent evolution of vocalization in echolocating mammals by potentially contributing to both rapid Ca2+transients and increased shortening velocities in superfast muscles.AbbreviationsSRsarcoplasmic reticulum
Expression of the Eight GABAA Receptor α Subunits in the Developing Zebrafish Central Nervous System
Authors: Monesson-Olson Bryan , McClain Jon J. , Case Abigail E. , Dorman Hanna E. , Turkewitz Daniel R. , Steiner Aaron B. , Downes Gerald B. 
Published: January 2018

ABSTRACTGABA is a robust regulator of both developing and mature neural networks. It exerts many of its effects through GABAA receptors, which are heteropentamers assembled from a large array of subunits encoded by distinct genes. In mammals, there are 19 different GABAA subunit types, which are divided into the α, β, γ, δ, ε, π, θ and ρ subfamilies. The immense diversity of GABAA receptors is not fully understood. However, it is known that specific isoforms, with their distinct biophysical properties and expression profiles, tune responses to GABA. Although larval zebrafish are well-established as a model system for neural circuit analysis, little is known about GABAA receptors diversity and expression in this system. Here, using database analysis, we show that the zebrafish genome contains at least 23 subunits. All but the mammalian θ and ε subunits have at least one zebrafish ortholog, while five mammalian GABAA subunits have two zebrafish orthologs. Zebrafish contain one subunit, β4, which does not have a clear mammalian ortholog. Similar to mammalian GABAA receptors, the zebrafish α subfamily is the largest and most diverse of the subfamilies. In zebrafish there are eight α subunits, and RNA in situ hybridization across early zebrafish development revealed that they demonstrate distinct patterns of expression in the brain, spinal cord, and retina. Some subunits were very broadly distributed, whereas others were restricted to small populations of cells. Subunit-specific expression patterns were similar between zebrafish, frogs and rodents, which suggests that the roles of different GABAA receptor isoforms are largely conserved among vertebrates. This study provides a platform to examine isoform specific roles of GABAA receptors within zebrafish neural circuits and it highlights the potential of this system to better understand the remarkable heterogeneity of GABAA receptors.
Quantification of double stranded DNA breaks and telomere length as proxies for corneal damage and replicative stress in 64 human keratoconus corneas
Authors: Wisse Robert PL , Kuiper Jonas JW , Radstake Timothy RDJ , Broen Jasper CA 
Published: January 2018

AbstractPurposeThe pathogenesis of keratoconus (KC) is multifactorial and associated with oxidative stress and subsequent DNA damage. The aim of this study was to investigate differences in DNA damage and replicative stress in patients with KC, and in both healthy and diseased controls.MethodsSixty-four corneal buttons were obtained from 27 patients with KC after corneal transplant surgery, 21 patients with a decompensated graft (DG), and 16 healthy controls (HC). The amount of intact Alu elements per genome copy as measured by qPCR was used to quantify intact DNA. Telomere length was measured as a proxy for replicative stress. In addition, telomerase reverse transcriptase(hTERT)gene expression level was assessed.ResultsMean (±SD) DNA damage was similar between the KC (5.56 ±14.08), DG (3.16 ±8.22), and HC (3.51 ±6.66) groups (P=0.807). No associations were found between DNA damage and patient age (P=0.523), atopic constitution (P=0.240), or contact lens wear (P=0.393). Telomere length differed (P=0.034), most notably in the KC group, andhTERTwas not detected in any corneal sample. Three cross-linked (CXL) KC corneas did not contain significant more DNA damage (2.6x,P =0.750).ConclusionsBased on these findings, differences in actual corneal DNA damage in KC could not be identified, and the longer telomere length in KC did not support replicative stress as a major etiological factor in the pathogenesis of KC. Future longitudinal investigations on KC etiology should assess progressive early cases to better comprehend the cellular and molecular processes preceding the archetypical morphological changes.PrecisOxidative stress is allegedly linked with the development of keratoconus. Whether these stressors actually lead to persisting DNA damage and replicative stress is debated. DNA damage was comparable with control samples, and a shortened telomere length was not identified.
Hidden partners: Using cross-docking calculations to predict binding sites for proteins with multiple interactions
Authors: Lagarde Nathalie , Carbone Alessandra , Sacquin-Mora Sophie 
Published: January 2018

AbstractProtein-protein interactions control a large range of biological processes and their identification is essential to understand the underlying biological mechanisms. To complement experimental approaches, in silico methods are available to investigate protein-protein interactions. Cross-docking methods, in particular, can be used to predict protein binding sites. However, proteins can interact with numerous partners and can present multiple binding sites on their surface, which may alter the binding site prediction quality. We evaluate the binding site predictions obtained using complete cross-docking simulations of 358 proteins with two different scoring schemes accounting for multiple binding sites. Despite overall good binding site prediction performances, 68 cases were still associated with very low prediction quality, presenting individual area under the specificity-sensitivity ROC curve (AUC) values below the random AUC threshold of 0.5, since cross-docking calculations can lead to the identification of alternate protein binding sites (that are different from the reference experimental sites). For the large majority of these proteins, we show that the predicted alternate binding sites correspond to interaction sites with hidden partners, i.e. partners not included in the original cross-docking dataset. Among those new partners, we find proteins, but also nucleic acid molecules. Finally, for proteins with multiple binding sites on their surface, we investigated the structural determinants associated with the binding sites the most targeted by the docking partners.AbbreviationsANOVA: ANalysis Of Variance; AUC: Area Under the Curve; Best Interface: BI; CAPRI: Critical Assessment of Prediction of Interactions; CC-D: Complete Cross-Docking; DNA: DesoxyriboNucleic Acid; FDR: False Discovery Rate; FRIres(type): Fraction of each Residue type in the Interface; FP: False Positives; GI: Global Interface; HCMD: Help Cure Muscular Dystrophy; JET: Joint Evolutionary Tree; MAXDo: Molecular Association via Cross Docking; NAI: Nucleic Acid Interface; NPV: Negative Predicted Value; PDB: Protein Data Bank; PIP: Protein Interface Propensity; PiQSi: Protein Quaternary Structure investigation; PPIs: Protein-Protein Interactions; PPV: Positive Predicted Value; Prec.: Precision; PrimI: Primary Interface; RNA: RiboNucleic Acid; ROC: Receiver Operating Characteristic; SecI: Secondary Interface; Sen.: Sensitivity; Spe.: Specificity; TN: True Negatives; TP: True Positives; WCG: World Community Grid.
Dynamic Flux Balance Analysis Models in SBML
Authors: König Matthias , Watanabe Leandro H. , Grzegorzewski Jan , Myers Chris J. 
Published: January 2018

ABSTRACTComputational models in systems biology and systems medicine are typically simulated using a single formalism such as ordinary differential equations (ODE). However, more complex models require the coupling of multiple formalisms since different biological phenomena are better described by different methods. For example, metabolism in steady state is often modeled using flux-balance analysis (FBA) whereas dynamic changes of model components are better described via ODEs. The coupling of FBA and ODE modeling formalisms results in dynamic FBA models. A major challenge is how to describe such hybrid models that couple multiple formalisms in a standardized way so that they can be exchanged between tools and simulated consistently in a reproducible manner. This paper presents a scheme for encoding and implementation of dynamic FBA models in the Systems Biology Markup Language (SBML), thereby enabling the exchange of multi-framework computational models between software tools. We demonstrate the feasibility of the approach using various example models and show that different tools are able to simulate the hybrid models and agree on the results. As part of this work, two independent implementations of a multi-framework simulation method for dynamic FBA have been developed supporting such models: iBioSim and sbmiutils.
Controlling for temporal discounting shifts rats from geometric to human-like arithmetic bisection
Authors: Kopec Charles D , Brody Carlos D 
Published: January 2018

AbstractHow our brains measure the passage of time is still largely open for debate. One behavioral task commonly used to study how durations are perceived is the Temporal Bisection Task, in which subjects categorize time durations as either “short” or “long.” The duration equally likely to be categorized as short or long is known as the bisection point. It has been consistently demonstrated that for humans, the bisection point is near the arithmetic mean of the longest and shortest durations the subject was trained on. In contrast, for non-human subjects it has been consistently found near the geometric mean. This difference implies that humans may process or represent temporal durations differently than other species. Here we present a behavioral model that reconciles the differences by demonstrating that rats’ performance on this task is driven not only by their noisy estimates of duration, but also by the temporally-discounted value of future rewards. The model correctly predicts shifts in the bisection point induced by unequal rewards and explains otherwise-paradoxical psychometric reversals documented three decades ago. Furthermore, as predicted by the model, we found that modifying the Temporal Bisection Task to eliminate the temporally-discounted reward component shifted the rats’ bisection point from the geometric mean to the arithmetic mean, thus bringing the rat results into line with the human results. We therefore propose that humans and rats (and perhaps other non-human subjects as well) process temporal information similarly, and that the difference between them in the Temporal Bisection Task may be simply due to rats weighing temporal discounting of future rewards more strongly than humans.