bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improvement in Patient-reported Hearing After Treatment With Bevacizumab in People With Neurofibromatosis Type 2
Authors: Huang Victoria , Bergner Amanda L. , Halpin Chris , Merker Vanessa L. , Sheridan Monica R. , Widemann Brigitte C. , Blakeley Jaishri O. , Plotkin Scott R. 
Published: April 2018

Objective:
Assess patient-reported outcomes (PRO) for hearing and tinnitus relative to clinical hearing assessment in people with neurofibromatosis 2 (NF2) associated hearing loss.

Study Design:
Prospective, open label, phase-II clinical trial with PRO administered pre-, post-, and after treatment.

Setting:
Three tertiary referral centers.

Patients:
Fourteen patients with NF2, median age of 30 years (range, 14–79 yr) and progressive hearing loss (median baseline word recognition score, 60%; range, 13–82%). Half of these patients achieved objective hearing response (word recognition score improved beyond the 95% critical difference versus baseline).

Intervention:
Bevacizumab 7.5 mg/kg was administered every 3 weeks for 48 weeks, followed by surveillance for 24 weeks off-drug.

Main Outcome Measures:
Speech, spatial, and qualities of hearing scale (SSQ) and tinnitus reaction questionnaire (TRQ) to assess hearing difficulties in life situations and tinnitus related distress.

Results:
Patient-reported speech understanding and auditory quality improved with bevacizumab treatment and were significantly correlated with word recognition scores, but not pure tone threshold average. There was no change in spatial perception after treatment. Reduction in tinnitus distress after treatment with bevacizumab did not reach statistical significance.

Conclusion:
Participants had reductions in hearing difficulty during treatment with bevacizumab, suggesting that patients subjectively experience hearing-related benefit mirroring clinical hearing assessments. We suspect the lack of significant reduction in tinnitus distress is related to small sample size and low intensity of distress in our sample. These data highlight the usefulness of PRO measures to assess benefits of treatment in the setting of NF2-associated hearing loss.
Oval Window Size and Shape: a Micro-CT Anatomical Study With Considerations for Stapes Surgery
Authors: Zdilla Matthew J. , Skrzat Janusz , Kozerska Magdalena , Leszczyński Bartosz , Tarasiuk Jacek , Wroński Sebastian 
Published: April 2018

Background:
The oval window is an important structure with regard to stapes surgeries, including stapedotomy for the treatment of otosclerosis. Recent study of perioperative imaging of the oval window has revealed that oval window niche height can indicate both operative difficulty and subjective discomfort during otosclerosis surgery. With regard to shape, structures incorporated into the oval window niche, such as cartilage grafts, must be compatible with the shape of the oval window. Despite the clinical importance of the oval window, there is little information regarding its size and shape.

Methods:
This study assessed oval window size and shape via micro-computed tomography paired with modern morphometric methodology in the fetal, infant, child, and adult populations. Additionally, the study compared oval window size and shape between sexes and between left- and right-sided ears.

Results:
No significant differences were found among traditional morphometric parameters among age groups, sides, or sexes. However, geometric morphometric methods revealed shape differences between age groups. Further, geometric morphometric methods provided the average oval window shape and most-likely shape variance.

Conclusion:
Beyond demonstrating oval window size and shape variation, the results of this report will aid in identifying patients among whom anatomical variation may contribute to surgical difficulty and surgeon discomfort, or otherwise warrant preoperative adaptations for the incorporation of materials into and around the oval window.
Sexually Transmitted Infection Prevalence in Women With HIV: Is There a Role for Targeted Screening?
Authors: Dionne-Odom Jodie , Westfall Andrew O. , Van Der Pol Barbara , Fry Karen , Marrazzo Jeanne 
Published: April 2018

Background
Rates of sexually transmitted infections (STIs) and HIV are highest in the southern United States but vary widely by sex, age, and risk behavior. Current guidelines recommend annual screening for chlamydia, gonorrhea, syphilis, and trichomoniasis in all sexually active women with HIV.

Methods
Screening rates and test positivity for chlamydia, gonorrhea, syphilis, and trichomoniasis were determined per calendar year in this retrospective cohort study of women in care at an urban HIV clinic in Birmingham, Alabama, from 2013 to 2015. Chlamydia, gonorrhea, and trichomonas infections were detected by molecular diagnostics and syphilis by serology. A combined end point for chlamydia/gonorrhea/syphilis (STI-3) was created based on similar test positivity and predictors. Predictors of STI-3 were identified using logistic regression and generalized estimating equations.

Results
Among 745 women with HIV, median age was 46.8 years, 78.8% were black, and 61% were sexually active. In 2015, 83.7% of women were tested for STI. Test positivity was 1.0% for chlamydia, 0.5% for gonorrhea, 1.6% for syphilis, and 13.3% for trichomoniasis. Independent predictors of STI-3 were recent chlamydia or gonorrhea (odds ratio [OR], 3.7; 95% confidence interval [CI], 1–13.4; P = 0.047), public insurance compared with private (OR, 3.5; CI, 1–11.8; P = 0.048), and sex after drugs/alcohol (OR, 3.0; CI, 1.2–8.0; P = 0.025). Women 50 years or older were less likely to have STI (OR, 0.3; CI, 0.1–1; P = 0.040).

Conclusions
In a cohort of women engaged in HIV care in the southern United States, detection of chlamydia, gonorrhea, and syphilis was infrequent but trichomoniasis was common. Many women screened for STI were low risk and universal testing strategies warrant evaluation.
Soluble Suppression Of Tumorigenicity-2 Predicts Hospital Mortality in Burn Patients: An Observational Prospective Cohort Pilot Study
Authors: Ruiz-Castilla Mireia , Bosacoma Pau , Dos Santos Bruce , Baena Jacinto , Guilabert Patricia , Marin-Corral Judith , Masclans Joan R. , Roca Oriol , Barret Juan P. 
Published: April 2018

ABSTRACT

Background:
The IL33/ST2 pathway has been implicated in the pathogenesis of different inflammatory diseases. Our aim was to analyze whether plasma levels of biomarkers involved in the IL33/ST2 axis might help to predict mortality in burn patients.

Methods:
Single-center prospective observational cohort pilot study performed at the Burns Unit of the Plastic and Reconstructive Surgery Department of the Vall d’Hebron University Hospital (Barcelona). All patients aged ≥18 years old with second or third-degree burns requiring admission to the Burns Unit were considered for inclusion. Blood samples were taken to measure levels of interleukins (IL)6, IL8, IL33, and soluble suppression of tumorigenicity-2 (sST2) within 24 h of admission to the Burns Unit and at day 3. Results are expressed as medians and interquartile ranges or as frequencies and percentages.

Results:
Sixty-nine patients (58 [84.1%] male, mean age 52 [35–63] years, total body surface area burned 21% [13%–30%], Abbreviated Burn Severity Index 6 [4–8]) were included. Thirteen (18.8%) finally died in the Burns Unit. Plasma levels of sST2 measured at day 3 after admission demonstrated the best prediction accuracy for survival (area under the receiver-operating curve 0.85 [0.71–0.99]; P < 0.001). The best cutoff point for the area under the receiver-operating curve index was estimated to be 2,561. In the Cox proportional hazards model, after adjusting for potential confounding, a plasma sST2 level ≥2,561 measured at day 3 was significantly associated with mortality (hazard ratio 6.94 [1.73–27.74]; P = 0.006).

Conclusions:
Plasma sST2 at day 3 predicts hospital mortality in burn patients.
MiRNA-Mediated Mechanisms of Cardiac Protection in Ischemic and Remote Ischemic Preconditioning—A Qualitative Systematic Review
Authors: Kohns Malte , Huhn Ragnar , Bauer Inge , Brandenburger Timo 
Published: April 2018

ABSTRACT

Background:
Ischemic preconditioning (IPC) and remote ischemic preconditioning (RIPC) protect myocardial tissue against subsequent ischemia and reperfusion injury (IRI) and have a high potential to improve patient outcome. The mediators and mechanisms of protection through IPC and RIPC remain largely unknown, but micro-RNAs (miRNAs) are promising candidates.

Methods:
Systematic review of Medline and Embase databases for biomedical scientific literature.

Results:
A total of 26 relevant publications (21 full-text original articles and 5 conference abstracts) were identified, 8 describing cell culture experiments, 14 animal experiments, and 4 randomized clinical trials in humans. Most commonly reported miRNAs with differential expression between preconditioned and control groups include miR-1, miR-21, and miR-144. Experimental designs and procedures differ widely, thereby limiting the potential to compare results between studies. Two of the four RCTs did not find any differentially expressed miRNAs.

Conclusions:
Results from RCTs should feed back into basic research and focused studies confirming or rejecting hypotheses generated by these RCTs are needed.
Characterisation of the UK honey bee (Apis mellifera) metagenome
Authors: Regan Tim , Barnett Mark W. , Laetsch Dominik R. , Bush Stephen J. , Wragg David , Budge Giles E. , Highet Fiona , Dainat Benjamin , de Miranda Joachim R. , Blaxter Mark , Freeman Tom C 
Published: April 2018

AbstractThe European honey bee (Apis mellifera) plays a major role in pollination and food production, but is under threat from emerging pathogens and agro-environmental insults. As with other organisms, honey bee health is a complex product of environment, host genetics and associated microbes (commensal, opportunistic and pathogenic). Improved understanding of bee genetics and their molecular ecology can help manage modern challenges to bee health and production. Sampling bee and cobiont genomes, we characterised the metagenome of 19 honey bee colonies across Britain. Low heterozygosity was observed in bees from many Scottish colonies, sharing high similarity to the native dark bee, A. mellifera mellifera. Apiaries exhibited high diversity in the composition and relative abundance of individual microbiome taxa. Most non-bee sequences derived from known honey bee commensal bacteria or known pathogens, e.g. Lotmaria passim (Trypanosomatidae), and Nosema spp. (Microsporidia). However, DNA was also detected from numerous additional bacterial, plant (food source), protozoan and metazoan organisms. To classify sequences from cobionts lacking genomic information, we developed a novel network analysis approach clustering orphan contigs, allowing the identification of a pathogenic gregarine. Our analyses demonstrate the power of high-throughput, directed metagenomics in agroecosystems identifying potential threats to honey bees present in their microbiota.
Lactobacillus acidophilusdisrupts collaborative multispecies bile acid metabolism
Authors: Dautel Sydney , Khan Nymul , Brandvold Kristoffer R. , Brislawn Colin J. , Hutchison Janine , Weitz Karl K. , Heyman Heino M. , Song Hyun-Seob , Ilhan Zehra Esra , Hill Eric A. , Hansen Joshua R. , Zheng Xueyun , Baker Erin S. , Cort John R. , Kim Young-Mo , Isern Nancy G. , DiBaise John K. , Krajmalnik-Brown Rosa , Jansson Janet K. , Wright Aaron T. , Metz Thomas O. , Bernstein Hans C. 
Published: April 2018

ABSTRACTBile acids are metabolic links between hosts and their gut microbiomes, yet little is known about the roles they play in microbe-to-microbe interactions. Here we present a study designed to investigate the effect that a common probiotic,Lactobacillus acidophilus, has on microbial interactions that lead to formation of secondary bile acids. A model microbial consortium was built from three human gut isolates,Clostridium scindens, Collinsella aerofaciens,andBlautia obeum, and cultured under different bile acid and probiotic treatments. A multi-omics platform that included mass spectrometry-based metabolomics and activity-based proteomic probes was used to produce two major results. The first, was that an uncommon secondary bile acid – ursocholate – was produced by a multi-species chemical synthesis pathway. This result highlights a new microbe-to-microbe interaction mediated by bile acids. The second finding was that the probiotic strain,L. acidophilus,quenched the observed interactions and effectively halted consortial synthesis of ursocholate. Little is known about the role that ursocholate plays in human health and development. However, we did discover that a decrease in ursocholate abundance corresponded with successful weight loss in patients after gastric bypass surgery versus those who did not lose weight after surgery. Hence, this study uncovered basic knowledge that may aid future designs of custom probiotic therapies to combat obesity.
Word selectivity in high-level visual cortex and reading skill
Authors: Kubota Emily C. , Joo Sung Jun , Huber Elizabeth , Yeatman Jason D. 
Published: April 2018

AbstractWord-selective neural responses in human ventral occipito-temporal cortex (VOTC) emerge as children learn to read, creating a visual word form area (VWFA) in the literate brain. It has been suggested that the VWFA arises through competition between pre-existing selectivity for other stimulus categories, changing the topography of VOTC to support rapid word recognition. Here, we hypothesized that competition between words and objects would be resolved as children acquire reading skill. Using functional magnetic resonance imaging (fMRI), we examined the relationship between responses to words and objects in VOTC in two ways. First, we defined the VWFA using a words > objects contrast and found that only skilled readers had a region that responded more to words than objects. Second, we defined the VWFA using a words > faces contrast and examined selectivity for words over objects in this region. We found that word selectivity strongly correlated with reading skill, suggesting reading skill-dependent tuning for words. Furthermore, we found that low word selectivity in struggling readers was not due to a lack of response to words, but to a high response to objects. Our results suggest that the fine-tuning of word-selective responses in VOTC is a critical component of skilled reading.
Levetiracetam and Rufinamide are effective at supressing spike and wave seizure activity in an in vitro model of absence epilepsy
Authors: Todorova Virdziniha , Ford Georgina , Traub Roger D. , Whittington Miles. A. , Hall Stephen. P. 
Published: April 2018

AbstractSpike-and-wave discharges (SpW) are seen in absence-type epilepsies. They are heterogeneous in terms of their clinical burden and their electrographic signature, which is used to classify different types of absence seizures; typical absence, in which SpW frequency is 3-4Hz and atypical absence, which shows a slower 1-2Hz frequency. Treatment of SpW varies dependent upon the syndrome, but both Valproic Acid (VPA) and Ethosuximide (ESM) are shown to be effective in controlling typical absence seizures. Other anti-epileptic’s (AED’s), Levetiracetam (LEV) and Rufinamide (RUF), have shown promise in treating absence epilepsies and their associated syndromes. Here we examine the efficacy of these AED’s on an in vitro model of SpW.Both LEV and RUF show an effective reduction in both the number of SpW events and the spike component amplitude; VPA shows no effect, whilst ESM enhances the spike amplitude. Phenytoin exacerbates the SpW activity, increasing both the number of SpW, amplitude of the SpW and the number of spikes within each event. These data suggest that both LEV and RUF could be effective in the treatment of absence-type epilepsies. They also suggest this model could be an effective tool to test other AED’s aimed at treating atypical absence syndromes.
Estimation of the cancer risk induced by rejuvenation therapy with young blood and treatment recommendations
Authors: Meyer-Hermann Michael 
Published: April 2018

AbstractIn recent years the transfer of blood from young to old individuals was shown to bear the potential of rejuvenation of stem cell activity. While this process might increase life expectancy by prolonging functionality of organs, higher cell replication rates bear also the risk of cancer. The extent of this risk is not known.While it is difficult to evaluate this cancer risk in experiments, this is possible with a mathematical model for tissue homeostasis by stem cell replication and associated cancer risk. The model suggests that young blood treatments can induce a substantial delay of organ failure with only minor increase in cancer risk. The benefit of rejuvenation therapy as well as the impact on cancer risk depend on the biological age at the time of treatment and on the overall cell turnover rate of the organs. Different organs have to be considered separately in the planning of the systemic treatment. In particular, the model predicts that the treatment schedules successfully applied in mice are not directly transferable to humans and guidelines for successful protocols are proposed. The model presented here may be used as a guidance for the development of treatment protocols.Additional informationThere is NO competing interests.
Opposing pupil responses to offered and anticipated reward values
Authors: Cash-Padgett Tyler , Azab Habiba , Michael Yoo Seng Bum , Hayden Benjamin Y. 
Published: April 2018

ABSTRACTPrevious studies have shown that the pupils dilate more in anticipation of larger rewards. This finding raises the possibility of a more general association between reward amount and pupil size. We tested this idea by characterizing macaque pupil responses to offered rewards during evaluation and comparison in a binary choice task. To control attention, we made use of a design in which offers occurred in sequence. By looking at pupil responses after choice but before reward, we confirmed the previously observed positive association between pupil size and anticipated reward values. Surprisingly, however, we find that pupil size is negatively correlated with the value of offered gambles before choice, during both evaluation and comparison stages of the task. These results demonstrate a functional distinction between offered and anticipated rewards, and present evidence against a narrow version of the simulation hypothesis, the idea that we represent offers by reactivating states associated with anticipating them. They also suggest that pupil size is correlated with relative, not absolute, values of offers, suggestive of an accept-reject model of comparison.
MicroRNAs reinforce repression of PRC2 transcriptional targets independently and through a feed-forward regulatory network
Authors: Shivram Haridha , Le Steven V. , Iyer Vishwanath R. 
Published: April 2018

AbstractGene expression can be regulated at multiple levels, but it is not known if and how there is broad coordination between regulation at the transcriptional and post-transcriptional levels. Transcription factors and chromatin regulate gene expression transcriptionally, while microRNAs (miRNAs) are small regulatory RNAs that function post-transcriptionally. Systematically identifying the post-transcriptional targets of miRNAs and the mechanism of transcriptional regulation of the same targets can shed light on regulatory networks connecting transcriptional and post-transcriptional control. We used iCLIP (individual crosslinking and immunoprecipitation) for the RISC (RNA-induced silencing complex) component AGO2 and global miRNA depletion to identify genes directly targeted by miRNAs. We found that PRC2 (Polycomb repressive complex 2) and its associated histone mark, H3K27me3, is enriched at hundreds of miRNA-repressed genes. We show that these genes are directly repressed by PRC2 and constitute a significant proportion of direct PRC2 targets. For just over half of the genes co-repressed by PRC2 and miRNAs, PRC2 promotes their miRNA-mediated repression by increasing expression of the miRNAs that are likely to target them. miRNAs also repress the remainder of the PRC2 target genes, but independently of PRC2. Thus, miRNAs post-transcriptionally reinforce silencing of PRC2-repressed genes that are inefficiently repressed at the level of chromatin, by either forming a feed-forward regulatory network with PRC2 or repressing them independently of PRC2.
Neuropathology and cognitive performance in centenarians
Authors: Ganz Andrea B. , Beker Nina , Hulsman Marc , Sikkes Sietske ,   NBB, Scheltens Philip , Smit August B. , Rozemuller Annemieke J. M. , Hoozemans Jeroen J.M. , Holstege Henne 
Published: April 2018

Abstract:With aging, the incidence of neuropathological hallmarks of neurodegenerative diseases increases in the brains of cognitively healthy individuals. It is currently unclear to what extent these hallmarks associate with symptoms of disease at extreme ages. Forty centenarians from the 100-plus Study cohort agreed to post-mortem brain donation. Centenarians self-reported to be cognitive healthy at baseline, which was confirmed by a proxy. Objective ante-mortem measurements of cognitive performance were associated with the prevalence, distribution and quantity of age- and AD-related neuropathological hallmarks. Despite self-reported cognitive health, objective neuropsychological testing suggested varying levels of ante-mortem cognitive functioning. Post-mortem, we found that most neuropathological hallmarks related to age and neurodegenerative diseases such as Aβ and Tau pathology, as well as atherosclerosis, were abundantly present in most or all centenarians, whereas Lewy body and pTDP-43 pathology were scarce. We observed that increased pathology loads correlated across pathology subtypes, and an overall trend of higher pathology loads to associate with a lower cognitive test performance. This trend was carried especially by the presence of neurofibrillary tangles (NFTs) and granulovacuolar degeneration (GVD) and to a lesser extent by Aβ-associated pathologies. Cerebral Amyloid Angiopathy (CAA) specifically associated with lower executive functioning in the centenarians. In conclusion, we find that while the centenarians in this cohort escaped or delayed cognitive impairment until extreme ages, their brains reveal varying levels of disease-associated neuropathological hallmarks, some of which associate with cognitive performance.
A catalog of single nucleotide changes distinguishing modern humans from archaic hominins
Authors: Kuhlwilm Martin , Boeckx Cedric 
Published: April 2018

AbstractThroughout the past decade, studying ancient genomes provided unique insights into human prehistory, and differences between modern humans and other branches like Neanderthals can enrich our understanding of the molecular basis of unique modern human traits. Modern human variation and the interactions between different hominin lineages are now well studied, making it reasonable to go beyond fixed changes and explore changes that are observed at high frequency in present-day humans. Here, we identify 571 genes with non-synonymous changes at high frequency. We suggest that molecular mechanisms in cell division and networks affecting cellular features of neurons were prominently modified by these changes. Complex phenotypes in brain growth trajectory and cognitive traits are likely influenced by these networks and other changes presented here. We propose that at least some of these changes contributed to uniquely human traits, and should be prioritized for experimental validation.