bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular determinants of metazoan tricRNA biogenesis
Authors: Schmidt Casey A , Giusto Joseph D , Bao Alicia , Hopper Anita K , Matera A Gregory 
Published: April 2019

AbstractMature tRNAs are generated by multiple post-transcriptional processing steps, which can include intron removal. Recently, we discovered a new class of circular non-coding RNAs in metazoans, called tRNA intronic circular (tric)RNAs. To investigate the mechanism of tricRNA biogenesis, we generated constructs that replace native introns of human and fruit fly tRNA genes with the Broccoli fluorescent RNA aptamer. Using these reporters, we identified cis-acting elements required for tricRNA formation in vivo. Disrupting a conserved base pair in the anticodon-intron helix dramatically reduces tricRNA levels. Although the integrity of this base pair is necessary for proper splicing, it is not sufficient. In contrast, strengthening weak bases in the helix also interferes with splicing and tricRNA production. Furthermore, we identified trans-acting factors important for tricRNA biogenesis, including several known tRNA processing enzymes such as the RtcB ligase and components of the TSEN endonuclease complex. Depletion of these factors inhibits Drosophila tRNA intron circularization. Notably, RtcB is missing from fungal genomes and these organisms normally produce linear tRNA introns. Here, we show that in the presence of ectopic RtcB, yeast lacking the tRNA ligase Rlg1/Trl1 are converted into producing tricRNAs. In summary, our work characterizes the major players in eukaryotic tricRNA biogenesis.
TAGOOS: genome-wide supervised learning of non-coding loci associated to complex phenotypes
Authors: González Aitor , Artufel Marie , Rihet Pascal 
Published: April 2019

Abstract
Genome-wide association studies (GWAS) associate single nucleotide polymorphisms (SNPs) to complex phenotypes. Most human SNPs fall in non-coding regions and are likely regulatory SNPs, but linkage disequilibrium (LD) blocks make it difficult to distinguish functional SNPs. Therefore, putative functional SNPs are usually annotated with molecular markers of gene regulatory regions and prioritized with dedicated prediction tools. We integrated associated SNPs, LD blocks and regulatory features into a supervised model called TAGOOS (TAG SNP bOOSting) and computed scores genome-wide. The TAGOOS scores enriched and prioritized unseen associated SNPs with an odds ratio of 4.3 and 3.5 and an area under the curve (AUC) of 0.65 and 0.6 for intronic and intergenic regions, respectively. The TAGOOS score was correlated with the maximal significance of associated SNPs and expression quantitative trait loci (eQTLs) and with the number of biological samples annotated for key regulatory features. Analysis of loci and regions associated to cleft lip and human adult height phenotypes recovered known functional loci and predicted new functional loci enriched in transcriptions factors related to the phenotypes.
In conclusion, we trained a supervised model based on associated SNPs to prioritize putative functional regions. The TAGOOS scores, annotations and UCSC genome tracks are available here: https://tagoos.readthedocs.io.
Balancing Operative Efficiency and Surgical Education: A Functional Neurosurgery Model
Authors: Rao Abigail J , Bullis Carli , Holste Katherine G , Teton Zoe , Burchiel Kim J , Raslan Ahmed M 
Published: April 2019

Abstract

BACKGROUND
Attending surgeons have dual obligations to deliver high-quality health care and train residents. In modern healthcare, lean principles are increasingly applied to processes preceding and following surgery. However, surgeons have limited data regarding variability and waste during any given operation.

OBJECTIVE
To measure variability and waste during the following key functional neurosurgery procedures: retrosigmoid craniectomy (microvascular decompression [MVD] and internal neurolysis) and deep brain stimulation (DBS). Additionally, we correlate variability with residents’ self-reported readiness for the surgical steps. The aim is to guide surgeons as they balance operative safety and efficiency with training obligations.

METHODS
For each operation (retrosigmoid craniectomy and DBS), a standard workflow, segmenting the operation into components, was defined. We observed a representative sample of operations, timing the components, with a focus on variability. To assess perceptions of safety and risk among surgeons of various training levels, a survey was administered. Survey results were correlated with operative variability, attempting to identify areas for increasing value without compromising trainee experience.

RESULTS
A sampling of each operation (n = 36) was observed during the study period. For MVD, craniectomy had the highest mean duration and standard deviation, whereas the MVD itself had the lowest mean duration and standard deviation. For DBS, the segments with largest standard deviation in duration were registration and electrode placement. For many steps of both procedures, there was a statistically significant relationship between increasing level of training and increasing perception of safety.

CONCLUSION
This proof-of-concept study introduces an educational and process-improvement tool that can be used to aid surgeons in increasing the efficiency of patient care.
Use of the Online Discussion Board in Health Professions Education: Contributions, Challenges, and Considerations
Authors: Donlan Pamela 
Published: April 2019

Abstract:Online discussion boards offer opportunities for individualized and interactive learning in higher education and are frequently used in health professions education. This article investigates the ways in which discussion board activities foster cognitive and affective domain learning among health professions students and contribute to the professional competencies that are required of emerging clinicians. In addition, pedagogical challenges, including the need to develop sophisticated interpersonal affective domain skills, promote problem-based learning, and prepare students for standardized examinations, are addressed. Considerations for practice, which include the importance of specific teaching strategies such as the shaping of student and instructor roles, scaffolding, and online debates and role-playing, are discussed.
“Beyond the Boundaries of Care Dependence”
Authors: Piredda Michela , Candela Maria L. , Mastroianni Chiara , Marchetti Anna , D’Angelo Daniela , Lusignani Maura , De Marinis Maria G. , Matarese Maria 
Published: April 2019

BackgroundDependence is a common life experience and innate condition for human beings due to their bodily and relational essence, but in contemporary society, it has become a stressful condition. Care dependence is central to nursing, and patients with advanced cancer are often dependent on care. Understanding nurses’ perceptions of care dependence can contribute to awareness of the impact it has on nurses.ObjectiveThe aim of this study was to explore palliative care nurses’ experiences and perceptions regarding patient dependence.MethodsSixteen nurses taking care of dependent patients in a palliative care center in Rome were interviewed. Giorgi’s descriptive phenomenological method was used.ResultsNurses caring for dependent patients transcend the boundaries of dependence. Care dependence is an experience of powerlessness and regression. A patient’s life in dependence is precarious, as they have to overcome the daily limits of life. Taking care of dependent patients requires nurses to manage the unmanageable and to know and to embrace change from within in order to build positive relations of personal closeness and reciprocal self-giving.ConclusionsNurses should be aware that self-transcendence and the consequent positive relations could make the difference in the experience of care dependence and promote personal growth for both patient and nurse. Positive and transcending relationships can transform care dependence into the opportunity to find meaning and purpose in life.Implications for PracticeThe study highlights what nurses feel in caring for dependent patients. Understanding nurses’ perceptions is important to delineate a proper caring for dependent patients.
Refinements in Otoplasty Surgery: Experience of 200 Consecutive Cases Using Cartilage-Sparing Technique
Authors: Mazeed Ahmed S. , Bulstrode Neil W. 
Published: April 2019

Background:
Many techniques have been described to correct prominent ears, including cartilage-suturing, cartilage-scoring, and cartilage-breaking techniques. Understanding the topography and anatomy of the auricular cartilage is crucial for performing safe otoplasty with consistent results.

Methods:
Two hundred consecutive patients with prominent ears were operated on using a modified Mustardé and Furnas technique with some refinements and without performing any cartilage scoring or excision. Adequate dissection and exposure of cartilage and precise repositioning of the tail of helix (cauda helicis) are keys to correction of lobule prominence without the need for any adjunctive procedures such as skin excision from the back of the lobule or suture fixation of the lobular tissues to the concha, mastoid, or scalp. Detailed description of the technique and review of the complications are presented.

Results:
This suturing-only technique had a low complication rate. Hematoma occurred in two patients only. Skin necrosis and wound dehiscence were not reported in any patient. Suture extrusion was the most common complication and was easily managed, mostly in the clinic. Relapse of deformity needing surgical correction occurred in eight cases.

Conclusions:
The series demonstrates that most of the potential complications of otoplasty can be avoided and favorable results can be obtained by paying attention to the anatomical details of the deformity and the auricular cartilage anatomy. The described cartilage-sparing otoplasty procedure with the refinements outlined resulted in a reproducible natural correction, with a low risk profile, that can be applied to almost all prominent ears.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Deconstructing a Leader: An In-Depth Analysis of the Commonalities between Plastic Surgery Chiefs and Chairmen
Authors: Wenzinger Eric , Weinstein Brielle , Singh Robinder , Reid Christopher M. , Suliman Ahmed , Herrera Fernando A. 
Published: April 2019

Background:
The authors sought to identify factors associated with current chiefs and chairpersons in academic plastic surgery to encourage and shape future leaders of tomorrow.

Methods:
Academic chairpersons in plastic surgery (n = 94) were identified through an Internet-based search of all Accreditation Council for Graduate Medical Education–accredited residency training programs during the year 2015. Sex, ethnicity, academic rank, board certification, time since certification, medical school attended, residency program attended, fellowships training, advanced degrees, obtaining leadership roles at trainee’s institution, and h-index were analyzed.

Results:
Of the 94 chiefs and chairpersons, 96 percent were male and 81 percent obtained full professor status, and 98 percent were certified by the American Board of Plastic Surgery. Mean time since certification was 22 years (range, 7 to 45 years). Fifty-one percent graduated from 20 medical schools, whereas 42 percent graduated from only nine plastic surgery training programs. Fifty-six percent had pursued fellowship beyond their primary plastic surgery training. Eighteen percent had obtained advanced degrees. Twenty-nine percent of chiefs and chairpersons obtained leadership roles at the institution where they had completed plastic surgery training. The mean h-index was 17.6 (range, 1 to 63). Graduates of the nine most represented residency programs had a mean h-index of 21 versus 15 when compared with the remaining chief/chairpersons (p < 0.0062).

Conclusion:
Leaders in plastic surgery are more likely to be male, hold academic rank of professor, and have completed a fellowship after residency.
Acute Adverse Reactions to Nonionic Iodinated Contrast Media
Authors: Suh Young Joo , Yoon Soon Ho , Hong Hyunsook , Hahn Seokyung , Kang Dong-Yoon , Kang Hye-Ryun , Choi Young-Hun , Lee Whal 
Published: April 2019

Objectives
We aimed to meta-analytically compare the incidence of acute adverse reactions (AARs) to nonionic iodinated contrast media (ICM) according to the type of ICM in patients who underwent radiologic examinations with administration of ICM via intravascular route.

Materials and Methods
A systematic literature search identified studies evaluating the incidence of AARs to 7 nonionic ICM (iobitridol, iohexol, iomeprol, iopamidol, iopromide, ioversol, and iodixanol) with extractable outcomes. These outcomes were pooled using a random-effects model, and the effect of ICM type on the incidence of overall and severe AARs was evaluated using meta-regression analysis.

Results
Thirty studies with 1,360,488 exposures to ICM were included. The pooled incidences of overall and severe AARs to nonionic ICM were 1.03% (95% confidence interval [CI], 0.81%–1.30%; I
2 = 0.99) and 0.0141% (95% CI, 0.0108%–0.0183%; I
2 = 0.56), respectively. Iomeprol had the highest overall AAR incidence (1.74%; 95% CI, 0.79%–3.76%; I
2 = 0.99), followed by iohexol (1.21%; 95% CI, 0.67%–2.17%; I
2 = 0.99), iopamidol (1.10%; 95% CI, 0.60%–2.03%; I
2 = 0.99), ioversol (0.88%; 95% CI, 0.43%–1.83%; I
2 = 0.96), iodixanol (0.85%; 95% CI, 0.36%–1.95%; I
2 = 0.99), iopromide (0.82%; 95% CI, 0.43%–1.55%; I
2 = 0.99), and iobitridol (0.77%; 95% CI, 0.36%–1.62%; I
2 = 0.99). Multivariable meta-regression analysis revealed that study design (P = 0.0014) and premedication (P = 0.0230) were statistically significant determinants affecting the incidence of overall AARs. Iodinated contrast media type did not affect the incidence of overall and severe AARs (P = 0.1453 and 0.4265, each).

Conclusions
The varying pooled incidences of overall and severe AARs to specific types of nonionic ICM do not remain as significant after adjusting confounders. Our results may support nonrestriction of certain types of nonionic ICM in the context of AAR avoidance.
Evaluating the Quality and Readability of Online Resources for Labiaplasty
Authors: Pandya Lopa K. , Hudson Catherine O. , Lynch Courtney D. , Nekkanti Silpa , Smith Pamela E. , Hundley Andrew F. 
Published: April 2019

Objectives
The aim of this study was to evaluate the quality, readability, and accuracy of Web-based information regarding labiaplasty and to characterize the types of Web sites providing this information.

Methods
Investigators used 3 major search engines to query the internet using the search terms labiaplasty, labia reduction, and vaginal rejuvenation. Two validated tools were used to evaluate Web sites: the JAMA benchmark tool and the DISCERN instrument. Three physicians independently reviewed each Web site. Interrater agreement was assessed, and reviewer scores were averaged. Flesch-Kincaid reading ease and Flesch-Kincaid grade level of each site were assessed. Data were analyzed using Stata 14.0 (College Station, TX).

Results
Of the 112 Web sites reviewed, 100 Web sites were from North America, 9 from Europe, 2 from Australia, and 1 from Asia. The median score using the JAMA tool was 1.0 (0.33–4.0), indicating low accountability, whereas the median score using the DISCERN tool was 28 (18.7–77) of 80 with higher scores indicating higher quality. Cohen’s weighted κ statistic (0.81) demonstrated near perfect agreement among reviewers for DISCERN scores. The median reading level was 11.9 (6.4–19.5). A majority of the Web sites (92) were for-profit businesses or blogs.

Conclusions
The internet enables patients to research sensitive topics and seek answers without worry of social stigma. Online health-related information is a widely used yet poorly studied source of medical information. The majority of Web sites reviewed lack balanced, evidence-based information. Given the wide variation in the quality of information, physicians should guide patients to reputable online resources.
Complete blood count with differential: An effective diagnostic for IBS subtype in the context of BMI?
Authors: Robinson JM , Boulineaux CM , Butler KR , Joseph PV , Murray MT , Pocock SN , Sherwin LB , Turkington SC , Weaver KR , Henderson WA 
Published: April 2019

AbstractThe Complete Blood Count with Differential hematological assay is a mainstay diagnostic for point-of-care clinical diagnoses for a spectrum of diseases including infection, inflammation, anemia, and leukemia, and CBC-D profiles are under investigation as early prognostic biomarkers for leukemias and other diseases. Chronic abdominal pain (CAP) and irritable bowel syndrome (IBS) are prevalent gastrointestinal disorders in the United States, with obesity among the most common comorbidities. Often, IBS-like gastrointestinal (GI) symptoms persist after resolution of known inflammation and/or enteropathogenic infection, and current literature contains significant discussion of the extent to which IBS is within the biological spectrum of inflammatory disease. Obesity is also associated with generalized signatures of inflammation and may confound accurate diagnoses. We performed ANOVA, multiple means comparisons, statistical analyses of CBC data from our "Brain-Gut Natural History" (BGNH) clinical cohort, with additional ELISA assays for lipopolysaccharide binding protein (LBP), IL-10, cortisol, and ACTH, signatures of immune-inflammatory response and Hypothalamic-Pituitary-Adrenal (HPA) axis activity, respectively. BGNH cohort includes healthy and overweight individuals diagnosed with IBS diarrhea-(IBS-D) and constipation-predominant (IBS-C) subtypes. We identified several potentially significant markers for IBS-D and IBS-C, notably IL-10, mean platelet volume (MPV), with LBP and monocyte percent also showing some statistical significance. Weight also showed significant results for overweight vs. normal weight, regardless of IBS subtype, particularly for Cortisol. CBC-D predictive profiles for IBS subtype and weight were identified using discriminant functions analysis and show that predictivity of marker profiles have poor performance relative to their normal weight subsets. Further refinement of this analysis will be performed utilizing increased sample size, additional molecular profiles, and enhanced statistical analysis.
Differential gene expression analysis reveals novel genes and pathways in pediatric septic shock patients
Authors: Mohammed Akram , Cui Yan , Mas Valeria R. , Kamaleswaran Rishikesan 
Published: April 2019

AbstractSeptic shock is a severe health condition caused by uncontrolled sepsis. Advancements in the high-throughput sequencing techniques have risen the number of potential genetic biomarkers under review. Multiple genetic markers and functional pathways play a part in the development and progression of pediatric septic shock. Fifty-four differentially expressed pediatric septic shock gene biomarkers were identified using gene expression data from 181 pediatric intensive care unit (PICU) patients within the first 24 hours of admission. The gene expression signatures discovered showed discriminatory power between pediatric septic shock survivors and nonsurvivors types. Using functional enrichment analysis of differentially expressed genes (DEGs), the known genes and pathways in septic shock were validated, and unexplored septic shock-related genes and functional groups were identified. Septic shock survivors were distinguished from septic shock non-survivors by differential expression of genes involved in the immune response, chemokine-mediated signaling, neutrophil chemotaxis, and chemokine activity. The identification of the septic shock gene biomarkers may facilitate in septic shock diagnosis, treatment, and prognosis.
Ablation of SUN2-containing LINC complexes drives cardiac hypertrophy without interstitial fibrosis
Authors: Stewart Rachel M. , Rodriguez Elisa C. , King Megan C. 
Published: April 2019

AbstractThe cardiomyocyte cytoskeleton, including the sarcomeric contractile apparatus, forms a cohesive network with cellular adhesions at the plasma membrane and nuclear-cytoskeletal linkages (LINC complexes) at the nuclear envelope. Human cardiomyopathies are genetically linked to the LINC complex and A-type lamins, but an full understanding of disease etiology in these patients is lacking. Here we show SUN2-null mice display cardiac hypertrophy coincident with enhanced AKT/MAPK signaling, as has been described previously for mice lacking A-type lamins. Surprisingly, in contrast to lamin A/C-null mice, SUN2-null mice fail to show coincident fibrosis or upregulation of pathological hypertrophy markers. Thus, cardiac hypertrophy is uncoupled from pro-fibrotic signaling in this mouse model, which we tie to a requirement for the LINC complex in productive TGFβ signaling. In the absence of SUN2, we detect elevated levels of the integral inner nuclear membrane protein MAN1, an established negative regulator of TGFβ signaling, at the nuclear envelope. We suggest that A-type lamins and SUN2 play antagonistic roles in the modulation of pro-fibrotic signaling through opposite effects on MAN1 levels at the nuclear lamina, suggesting a new perspective on disease etiology.
A model for estimating traction force magnitude reveals differential regulation of actomyosin activity and matrix adhesion number in response to smooth muscle cell spreading
Authors: Ahmed Sultan , Mabeza Panashe , Warren Derek T 
Published: April 2019

AbstractDecreased aortic compliance is associated with ageing and vascular disease, including atherosclerosis and hypertension. Ultimately, changes in aortic compliance are driven by altered ECM composition however, recent findings have identified a cellular component to decreased aortic compliance observed in ageing and hypertension. Vascular smooth muscle cells (VSMCs) line the blood vessel wall and VSMC contraction regulates vascular tone and contributes to aortic compliance. Mechanical cues derived from the ECM influence VSMC function, yet whether ECM rigidity influences VSMC force generation remains unclear. In this study, we describe the relationship between VSMC spreading, traction force magnitude and matrix rigidity. Importantly, we show that spreading predicts integrated traction force (integrated-TF) magnitude independently of matrix rigidity. Using linear regression analysis, we have generated a model for calculating integrated-TF from VSMC area. This model closely predicts the integrated traction force measured by live VSMC traction force microscopy. Vinculin staining analysis revealed that spreading strongly correlated with adhesion number per VSMC, suggesting that increased VSMC integrated-TF was due to enhanced matrix anchor points. Further analysis revealed that calculated integrated-TF per adhesion was reduced by matrix rigidity, however, adhesion number/μm2increased, resulting in the average integrated-TF/μm2remaining unaltered. As a result, the integrated-TF/VSMC spreading relationship is independent of matrix rigidity. Therefore, our study has identified and validated a novel model to predict and understand the mechanisms influencing VSMC traction force magnitude.