bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Lipid- Versus Sodium Hyaluronate-Containing Eye Drops on Optical Quality and Ocular Surface Parameters as a Function of the Meibomian Gland Dropout Rate
Authors: Miháltz Kata , Faschinger Eva Maria , Vécsei-Marlovits Pia Veronika 
Published: January 2018

Purpose:
To evaluate the effect of lipid- versus sodium hyaluronate-based eye drops on optical quality and ocular surface parameters.

Methods:
Sixty eyes of 30 patients with mild-to-moderate dry eye disease were included in a prospective randomized study. Each patient received either lipid- or sodium hyaluronate-based eye drops. Ocular symptom scores, breakup time, Schirmer test, fluorescein staining, noncontact meibography, and aberrometry were evaluated before and after 3 months of therapy.

Results:
At the 3-month visit, a statistically significant improvement (P ≤ 0.05) was noted in both groups on the Schirmer test, breakup time, ocular surface staining, and symptom score. In the lipid group, patients with progressive meibomian gland (MG) loss (>50%) showed a significantly greater increase in their corneal higher-order (HO) Strehl ratio (0.25 ± 0.26 vs. −0.01 ± 0.25, P = 0.02) and modulation transfer function (MTF) (0.12 ± 0.17 vs. −0.02 ± 0.06, P = 0.03) than patients with less advanced MG disease. In the lipid group, a significant positive correlation was noted between the MG dropout rate and improvement in Schirmer values [Spearman correlation coefficient (CC): 0.79], corneal HO Strehl (CC: 0.75), and HO modulation transfer function (CC: 0.6), but a significant negative correlation was noted between the MG dropout rate and the HO root mean square (CC: −0.73).

Conclusions:
Lipid-containing artificial tears seem to be superior to sodium hyaluronate-containing drops in terms of improving HO aberrations and optical quality in patients with significant MG dysfunction.
Nomogram to Predict Graft Thickness in Descemet Stripping Automated Endothelial Keratoplasty: An Eye Bank Study
Authors: Bae Steven S. , Menninga Isaac , Hoshino Richard , Humphreys Christine , Chan Clara C. 
Published: January 2018

Purpose:
The purpose of this study was to develop a nomogram to predict postcut thickness of corneal grafts prepared at an eye bank for Descemet stripping automated endothelial keratoplasty (DSAEK).

Methods:
Retrospective chart review was performed of DSAEK graft preparations by 3 experienced technicians from April 2012 to May 2017 at the Eye Bank of Canada—Ontario Division. Variables collected included the following: donor demographics, death-to-preservation time, death-to-processing time, precut tissue thickness, postcut tissue thickness, microkeratome head size, endothelial cell count, cut technician, and rate of perforation. Linear regression models were generated for each microkeratome head size (300 and 350 μm).

Results:
A total of 780 grafts were processed during the study period. Twelve preparation attempts resulted in perforation (1.5%) and were excluded. Mean precut tissue thickness was 510 ± 49 μm (range: 363–670 μm). Mean postcut tissue thickness was 114 ± 22 μm (range: 57–193 μm). Seventy-nine percent (608/768) of grafts were ≤130 μm. The linear regression models included precut thickness and donor age, which were able to predict the thickness to within 25 μm 80% of the time.

Conclusions:
We report a nomogram to predict thickness of DSAEK corneal grafts prepared in an eye bank setting, which was accurate to within 25 μm 80% of the time. Other eye banks could consider performing similar analyses.
Metacognitive Interpersonal Therapy for Personality Disorders Featuring Emotional Inhibition
Authors: Gordon-King Keely , Schweitzer Robert D. , Dimaggio Giancarlo 
Published: January 2018

Abstract
Metacognitive interpersonal therapy (MIT) is an integrative psychotherapeutic approach targeting personality disorders (PDs) featuring inhibition and avoidance. The current case series reports the outcome of a time-limited, 12-month MIT intervention for people with PDs featuring emotional inhibition. Seven participants were diagnosed with a PD on the basis of a structured clinical interview. The study followed a multiple baseline design, with baseline measures taken for 3 weeks before intervention. Participants underwent 12 months of weekly MIT sessions, with outcome measures taken every 3 months. Outcome variables were diagnostic recovery, symptom severity, and alexithymia. All participants improved over the course of the 12-month intervention across most measures. For six of the participants, the intervention was a likely driver of change. The current study contributes to a growing evidence base regarding the effectiveness of MIT for the treatment of PDs.
ICD-11 Prevalence Rates of Posttraumatic Stress Disorder and Complex Posttraumatic Stress Disorder in a German Nationwide Sample
Authors: Maercker Andreas , Hecker Tobias , Augsburger Mareike , Kliem Sören 
Published: January 2018

Abstract
Prevalence rates are still lacking for posttraumatic stress disorder (PTSD) and complex PTSD (CPTSD) diagnoses based on the new ICD-11 criteria. In a nationwide representative German sample (N = 2524; 14–99 years), exposure to traumatic events and symptoms of PTSD or CPTSD were assessed with the International Trauma Questionnaire. A clinical variant of CPTSD with a lower threshold for core PTSD symptoms was also calculated, in addition to conditional prevalence rates dependent on trauma type and differential predictors. One-month prevalence rates were as follows: PTSD, 1.5%; CPTSD, 0.5%; and CPTSD variant, 0.7%. For PTSD, the highest conditional prevalence was associated with kidnapping or rape, and the highest CPTSD rates were associated with sexual childhood abuse or rape. PTSD and CPTSD were best differentiated by sexual violence. Combined PTSD and CPTSD (ICD-11) rates were in the range of previously reported prevalences for unified PTSD (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition; ICD-10). Evidence on differential predictors of PTSD and CPTSD is still preliminary.
Mycoplasma genitalium Infection in Kenyan and US Women
Authors: Balkus Jennifer E. , Manhart Lisa E. , Jensen Jørgen S. , Anzala Omu , Kimani Joshua , Schwebke Jane , Shafi Juma , Rivers Charles , Kabare Emanuel , McClelland R. Scott 
Published: January 2018

Background
Little is known about the natural history of Mycoplasma genitalium (MG) infection in women. We retrospectively tested archived vaginal fluid samples to assess MG prevalence, incidence, persistence, recurrence and antimicrobial resistance markers among women participating in the Preventing Vaginal Infections trial, a randomized trial of monthly presumptive treatment to reduce vaginal infections.

Methods
High-risk, nonpregnant, HIV-negative women aged 18 to 45 years from Kenya and the United States were randomized to receive metronidazole 750 mg + miconazole 200 mg intravaginal suppositories or placebo for 5 consecutive nights each month for 12 months. Clinician-collected swabs containing cervicovaginal fluid were tested for MG using Hologic nucleic acid amplification testing at enrollment and every other month thereafter. Specimens that were MG+ underwent additional testing for macrolide resistance–mediating mutations by DNA sequencing.

Results
Of 234 women enrolled, 221 had available specimens and 25 (11.3%) had MG at enrollment. Among 196 women without MG at enrollment, there were 52 incident MG infections (incidence, 33.4 per 100 person-years). Smoking was independently associated with incident MG infection (adjusted hazard ratio, 3.02; 95% confidence interval, 1.32–6.93), and age less than 25 years trended toward an association (adjusted hazard ratio, 1.70; 95% confidence interval, 0.95–3.06). Median time to clearance of incident MG infections was 1.5 months (interquartile range, 1.4–3.0 months). Of the 120 MG+ specimens, 16 specimens from 15 different women were macrolide resistance–mediating mutation positive (13.3%), with no difference by country.

Conclusions

M. genitalium infection is common among sexually active women in Kenya and the Southern United States. Given associations between MG and adverse reproductive health outcomes, this high burden of MG in reproductive-aged women could contribute to substantial morbidity.
Validity Evidence for a Serious Game to Assess Performance on Critical Pediatric Emergency Medicine Scenarios
Authors: Gerard James M. , Scalzo Anthony J. , Borgman Matthew A. , Watson Christopher M. , Byrnes Chelsie E. , Chang Todd P. , Auerbach Marc , Kessler David O. , Feldman Brian L. , Payne Brian S. , Nibras Sohail , Chokshi Riti K. , Lopreiato Joseph O. 
Published: January 2018

Introduction
We developed a first-person serious game, PediatricSim, to teach and assess performances on seven critical pediatric scenarios (anaphylaxis, bronchiolitis, diabetic ketoacidosis, respiratory failure, seizure, septic shock, and supraventricular tachycardia). In the game, players are placed in the role of a code leader and direct patient management by selecting from various assessment and treatment options. The objective of this study was to obtain supportive validity evidence for the PediatricSim game scores.

Methods
Game content was developed by 11 subject matter experts and followed the American Heart Association's 2011 Pediatric Advanced Life Support Provider Manual and other authoritative references. Sixty subjects with three different levels of experience were enrolled to play the game. Before game play, subjects completed a 40-item written pretest of knowledge. Game scores were compared between subject groups using scoring rubrics developed for the scenarios. Validity evidence was established and interpreted according to Messick's framework.

Results
Content validity was supported by a game development process that involved expert experience, focused literature review, and pilot testing. Subjects rated the game favorably for engagement, realism, and educational value. Interrater agreement on game scoring was excellent (intraclass correlation coefficient = 0.91, 95% confidence interval = 0.89–0.9). Game scores were higher for attendings followed by residents then medical students (P
c < 0.01) with large effect sizes (1.6–4.4) for each comparison. There was a very strong, positive correlation between game and written test scores (r = 0.84, P < 0.01).

Conclusions
These findings contribute validity evidence for PediatricSim game scores to assess knowledge of pediatric emergency medicine resuscitation.
Gender, Race and Disease Etiology Predict De Novo Malignancy Risk After Liver Transplantation: Insights for Future Individualized Cancer Screening Guidance
Authors: Bhat Mamatha , Mara Kristin , Dierkhising Ross , Watt Kymberly D. 
Published: January 2018

Background
Malignancy after liver transplant (LT) is a leading cause of mortality, but data is limited. The aim of this study was to identify patients at higher risk for de novo malignancies after LT in a large multicenter database.

Methods
The Scientific Registry of Transplant Recipients database comprising all 108 412 LT recipients across the United States between 1987 and March 2015 was analyzed with a median follow-up of 6.95 years. Potential risk factors for malignancies after LT were assessed using Cox regression analysis for the outcome of time to first malignancy.

Results
Mean age 51.9 ± 10.8 years, 64.6% male, 74.5% white, and 15.8% with previous malignancy. Malignancies during follow-up were 4,483 (41.3%) skin, 1519 (14.0%) hematologic, and 4842 (44.7%) solid organ. The 10-year probability of de novo malignancy was 11.5% (11.3-11.8%). On multivariable analysis, age by decade (hazard ratio [HR], 1.52; P < 0.001), male sex (HR, 1.28; P < 0.001), white race (compared with other races: HR, 1.45-2.04; P < 0.001), multiorgan transplant (HR, 1.35; P < 0.001), previous malignancy (HR, 1.34; P < 0.001), and alcoholic liver disease, autoimmune, nonalcoholic steatohepatitis (HR, 1.35; P < 0.001), and primary sclerosing cholangitis pre-LT (compared with hepatitis C virus, P < 0.001) were associated with higher risk of post-LT malignancy, but type of immunosuppression was not (P = NS).

Conclusions
This large data set demonstrates the effects of ethnicity/race and etiologies of liver disease, particularly nonalcoholic steatohepatitis as additional risk factors for cancer after LT. Patients with these high-risk characteristics should be more regularly and diligently screened.
Intrinsic functional reorganisation of the attention network in the blind
Authors: Qin Wen , Liu Yong , Jiang Tianzi , Yu Chunshui 
Published: January 2018

AbstractAttention can bias visual perception by modulating the neuronal activity of visual areas. However, little is known if blindness can reshape the intrinsic functional organisation within the attention networks and between the attention and visual networks. A voxel-wise network-based functional connectivity strengthen mapping analysis was proposed to thirty congenitally, thirty early and thirty late blind subjects, and thirty sighted controls. Both the blind and sighted subjects exhibited similar spatial distributions of the intrinsic dorsal (DAN) and ventral (VAN) attention networks. Moreover, compared to the sighted controls, the blind subjects showed increased functional coupling within the DAN, and between the DAN and VAN, and between the attention sub-networks and visual areas, suggesting an increased information communication by visual deprivation. However, the onset age of blindness had little impact on the functional coupling of the attention network, indicating that non-visual sensory experience is enough for driving the development of intrinsic functional organization of the attention network. Finally, a positive correlation was identified between the duration of blindness and the functional coupling of the posterior inferior frontal gyrus with the visual network, representing an experience-dependent reorganisation after visual deprivation.
Metabolic mechanisms of interaction within a defined gut microbiota
Authors: Medlock Gregory L. , Carey Maureen A. , McDuffie Dennis G. , Mundy Michael B. , Giallourou Natasa , Swann Jonathan R. , Kolling Glynis L. , Papin Jason A. 
Published: January 2018

AbstractMetabolic interactions among species are ubiquitous in nature, and the fitness costs and benefits they impose often reinforce and stabilize them over time. These interactions are of particular importance in the human gut, where they have functions ranging from enhancing digestion to preventing (or exacerbating) infections. The diversity and sheer number of species present lead to the potential for a multitude of metabolic interactions among species to occur. However, identifying the mechanism and consequences of metabolic interactions between even two species is incredibly challenging. Here, we develop, apply, and experimentally test a framework for identifying potential metabolic mechanisms associated with interspecies interactions. We perform pairwise growth and metabolome profiling of co-cultures of strains from the altered Schaedler flora (ASF), a defined murine microbiota. We then apply our novel framework, which we call the Constant Yield Expectation (ConYE) model, to dissect emergent metabolic behaviors that occur in co-culture. Using the ConYE model, we identify and interrogate an amino acid cross-feeding interaction that is likely to confer a growth benefit to one ASF strain (Clostridium sp. ASF356) in co-culture with another strain (Parabacteroides goldsteinii ASF519). We experimentally validate that the proposed interaction leads to a growth benefit for this strain via media supplementation experiments. Our results reveal the type and extent of emergent metabolic behavior in microbial communities and demonstrate how metabolomic data can be used to identify potential metabolic interactions between organisms such as gut microbes. Ourin vitrocharacterization of the ASF strains and interactions between them also enhances our ability to interpret and design experiments that utilize ASF-colonized animals. We anticipate that this work will improve the tractability of studies utilizing mice colonized with the ASF. Here, we focus on growth-modulating interactions, but the framework we develop can be applied to generate specific hypotheses about mechanisms of interspecies interaction involved in any phenotype of interest within a microbial community.
Atlas of Transcription Factor Binding Sites from ENCODE DNase Hypersensitivity Data Across 27 Tissue Types
Authors: Funk Cory C. , Casella Alex M. , Jung Segun , Richards Matthew A. , Rodriguez Alex , Shannon Paul , Donovan-Maiye Rory , Heavner Ben , Chard Kyle , Xiao Yukai , Glusman Gustavo , Ertekin-Taner Nilufer , Golde Todd E. , Toga Arthur , Hood Leroy , Van Horn John D. , Kesselman Carl , Foster Ian , Madduri Ravi , Price Nathan D. , Ament Seth A. 
Published: January 2018

AbstractThere is intense interest in mapping the tissue-specific binding sites of transcription factors in the human genome to reconstruct gene regulatory networks and predict functions for non-coding genetic variation. DNase-seq footprinting provides a means to predict genome-wide binding sites for hundreds of transcription factors (TFs) simultaneously. However, despite the public availability of DNase-seq data for hundreds of samples, there is neither a unified analytical workflow nor a publicly accessible database providing the locations of footprints across all available samples. Here, we implemented a workflow for uniform processing of footprints using two state-of-the-art footprinting algorithms: Wellington and HINT. Our workflow scans the footprints generated by these algorithms for 1,530 sequence motifs to predict binding sites for 1,515 human transcription factors. We applied our workflow to detect footprints in 192 DNase-seq experiments from ENCODE spanning 27 human tissues. This collection of footprints describes an expansive landscape of potential TF occupancy. At thresholds optimized through machine learning, we report high-quality footprints covering 9.8% of the human genome. These footprints were enriched for true positive TF binding sites as defined by ChIP-seq peaks, as well as for genetic variants associated with changes in gene expression. Integrating our footprint atlas with summary statistics from genome-wide association studies revealed that risk for neuropsychiatric traits was enriched specifically at highly-scoring footprints in human brain, while risk for immune traits was enriched specifically at highly-scoring footprints in human lymphoblasts. Our cloud-based workflow is available at github.com/globusgenomics/genomics-footprint and a database with all footprints and TF binding site predictions are publicly available at http://data.nemoarchive.org/other/grant/sament/sament/footprint_atlas.
An atypical CRISPR-Cas locus in Symbiobacterium thermophilum flanked by a transposase, a reverse transcriptase, the endonuclease MutS2 and a putative Cas9-like protein
Authors: Chakraborty Sandeep 
Published: January 2018

AbstractClustered regularly interspaced short palindromic repeats (CRISPR) is a prokaryotic adaptive defense system that assimilates short sequences of invading genomes (spacers) within repeats, and uses nearby effector proteins (Cas), one of which is an endonuclease (Cas9), to cleave homologous nucleic acid during future infections from the same or closely related organisms. Here, a novel CRISPR locus with uncharacterized Cas proteins, is reported in Symbiobacterium thermophilum (Accid:NC 006177.1) around loc.1248561. Credence to this assertion is provided by four arguments. First, the presence of an exact repeat (CACGTGGGGTTCGGGTCGGACTG, 23 nucleotides) occurs eight times encompassing fragments about 83 nucleotides long. Second, comparison to a known CRISPR-Cas locus in the same organism (loc.355482) with an endonuclease Cas3 (WP 011194444.1, 729 aa) ∼10000 nt upstream shows the presence of a known MutS2 endonuclease (WP 011195247.1, 801 aa) in approximately the same distance in loc.1248561. Thirdly, and remarkably, an uncharacterized protein (1357 aa) long is uncannily close in length to known Cas9 proteins (1368 for Streptococcus pyogenes). Lastly, the presence of transposases and reverse transcriptase (RT) downstream of the repeat indicates this is one of an enigmatic RT-CRISPR locus, Also, the MutS2 endonuclease is not characterized as a CRISPR-endonuclease to the best of my knowledge. Interestingly, this locus was not among the four loci (three confirmed, one probable) reported by crisperfinder (http://crispr.i2bc.paris-saclay.fr/Server), indicating that the search algorithm needs to be revisited. This finding begs the question ‐ how many such CRISPR-Cas loci and Cas9-like proteins lie undiscovered within bacterial genomes?
On the design of CRISPR-based single cell molecular screens
Authors: Hill Andrew J. , McFaline-Figueroa José L. , Starita Lea M. , Gasperini Molly J. , Matreyek Kenneth A. , Packer Jonathan , Jackson Dana , Shendure Jay , Trapnell Cole 
Published: January 2018

AbstractSeveral groups recently reported coupling CRISPR/Cas9 perturbations and single cell RNA-seq as a potentially powerful approach for forward genetics. Here we demonstrate that vector designs for such screens that rely on cis linkage of guides and distally located barcodes suffer from swapping of intended guide-barcode associations at rates approaching 50% due to template switching during lentivirus production, greatly reducing sensitivity. We optimize a published strategy, CROP-seq, that instead uses a Pol II transcribed copy of the sgRNA sequence itself, doubling the rate at which guides are assigned to cells to 94%. We confirm this strategy performs robustly and further explore experimental best practices for CRISPR/Cas9-based single cell molecular screens.
Thermodynamic analysis of mitochondrial DNA breakpoints reveals mechanistic details of deletion mutagenesis
Authors: Lakshmanan Lakshmi Narayanan , Yee Zhuangli , Gruber Jan , Halliwell Barry , Gunawan Rudiyanto 
Published: January 2018

AbstractBroad evidence support double-strand breaks (DSBs) as initiators of mitochondrial DNA (mtDNA) deletion mutations. But the mechanism of DSB-induced deletions, including the DSB repair pathway(s) involved, remains to be established. Here, we used DNA hybridization thermodynamics to analyze misalignment lengths surrounding deletion breakpoints. Our analysis of 9,655 previously reported mammalian mtDNA deletions and 1,307 novel Caenorhabditis elegans mtDNA deletions, indicates a significant role of 0–25bp misalignments, supporting the role of erroneous non-homologous and micro-homology dependent DSB repair in deletion formation. Based on these insights we propose that DSB-induced mtDNA deletions occur via the misjoining of DSB ends and/or strand invasion of open mtDNA regions by DSB ends.