bluuebunny/crossref_metadata_2025 huggingface dataset:
Unplanned Reoperation After Craniotomy for Tumor: A National Surgical Quality Improvement Program Analysis
Authors: Dasenbrock Hormuzdiyar H , Yan Sandra C , Chavakula Vamsi , Gormley William B , Smith Timothy R , Claus Elizabeth B , Dunn Ian F
Published: April 2017

BACKGROUND

Reoperation has been increasingly utilized as a metric evaluating quality of care.

OBJECTIVE

To evaluate the rate of, reasons for, and predictors of unplanned reoperation after craniotomy for tumor in a nationally accrued population.

METHODS

Patients who underwent cranial tumor resection were extracted from the prospective National Surgical Quality Improvement Program registry (2012-2014). Multivariate logistic regression examined predictors of unplanned cranial reoperation. Predictors screened included patient age, sex, tumor location and histology, functional status, comorbidities, preoperative laboratory values, operative urgency, and time.

RESULTS

Of the 11 462 patients included, 3.1% (n = 350) underwent an unplanned cranial reoperation. The most common reasons for cranial reoperation were intracranial hematoma evacuation (22.5%), superficial or intracranial surgical site infections (11.9%), re-resection of tumor (8.4%), decompressive craniectomy (6.1%), and repair of cerebrospinal fluid leakage (5.6%). The strongest predictor of any cranial reoperation was preoperative thrombocytopenia (less than 100 000/μL, odds ratio [OR] = 2.51, 95% confidence interval [CI]: 1.23-5.10, P = .01). Thrombocytopenia, hypertension, emergent surgery, and longer operative time were predictors of reoperation for hematoma (P ≤ .004), while dependent functional status, morbid obesity, leukocytosis, and longer operative time were predictors of reoperation for infection (P < .05). Although any unplanned cranial reoperation was not associated with differential odds of mortality (OR = 1.68, 95% CI: 0.94-3.00, P = .08), hematoma evacuation was significantly associated with thirty-day death (P = .04).

CONCLUSION

In this national analysis, unplanned cranial reoperation was primarily associated with operative indices, rather than preoperative characteristics, suggesting that reoperation may have some utility as a quality indicator. However, hypertension and thrombocytopenia were potentially modifiable predictors of reoperation.
Outpatient vs Inpatient Anterior Cervical Discectomy and Fusion: A Population-Level Analysis of Outcomes and Cost
Authors: Purger David A , Pendharkar Arjun V , Ho Allen L , Sussman Eric S , Yang Lingyao , Desai Manisha , Veeravagu Anand , Ratliff John K , Desai Atman
Published: April 2017

BACKGROUND

Outpatient anterior cervical discectomy and fusion (ACDF) is a promising candidate for US healthcare cost reduction as several studies have demonstrated that overall complications are relatively low and early discharge can preserve high patient satisfaction, low morbidity, and minimal readmission.

OBJECTIVE

To compare clinical outcomes and associated costs between inpatient and ambulatory setting ACDF.

METHODS

Demographics, comorbidities, emergency department (ED) visits, readmissions, reoperation rates, and 90-d charges were retrospectively analyzed for patients undergoing elective ACDF in California, Florida, and New York from 2009 to 2011 in State Inpatient and Ambulatory Databases.

RESULTS

A total of 3135 ambulatory and 46 996 inpatient ACDFs were performed. Mean Charlson comorbidity index, length of stay, and mortality were 0.2, 0.4 d, and 0% in the ambulatory cohort and 0.4, 1.8 d, and 0.04% for inpatients (P < .0001). Ambulatory patients were younger (48.0 vs 53.1) and more likely to be Caucasian. One hundred sixty-eight ambulatory patients (5.4%) presented to the ED within 30 d (mean 11.3 d), 51 (1.6%) were readmitted, and 5 (0.2%) underwent reoperation. Among inpatient surgeries, 2607 patients (5.5%) presented to the ED within 30 d (mean 9.7 d), 1778 (3.8%) were readmitted (mean 6.3 d), and 200 (0.4%) underwent reoperation. Higher Charlson comorbidity index increased rate of ED visits (ambulatory operating room [OR] 1.285, P < .05; inpatient OR 1.289, P < .0001) and readmission (ambulatory OR 1.746, P < .0001; inpatient OR 1.685, P < .0001). Overall charges were significantly lower for ambulatory ACDFs ($33 362.51 vs $74 667.04; P < .0001).

CONCLUSION

ACDF can be performed in an ambulatory setting with comparable morbidity and readmission rates, and lower costs, to those performed in an inpatient setting.
Safety Aspects of Postanesthesia Care Unit Discharge without Motor Function Assessment after Spinal Anesthesia
Authors: Aasvang Eske Kvanner , Jørgensen Christoffer Calov , Laursen Mogens Berg , Madsen Jacob , Solgaard Søren , Krøigaard Mogens , Kjærsgaard-Andersen Per , Mandøe Hans , Hansen Torben Bæk , Nielsen Jørgen Ulrich , Krarup Niels , Skøtt Annette Elisabeth , Kehlet Henrik
Published: April 2017

Background

Postanesthesia care unit (PACU) discharge without observation of lower limb motor function after spinal anesthesia has been suggested to significantly reduce PACU stay and enhance resource optimization and early rehabilitation but without enough data to allow clinical recommendations.

Methods

A multicenter, semiblinded, noninferiority randomized controlled trial of discharge from the PACU with or without assessment of lower limb motor function after elective total hip or knee arthroplasty under spinal anesthesia was undertaken. The primary outcome was frequency of a successful fast-track course (length of stay 4 days or less and no 30-day readmission). Noninferiority would be declared if the odds ratio (OR) for a successful fast-track course was no worse for those patients receiving no motor function assessment versus those patients receiving motor function assessment by OR = 0.68.

Results

A total of 1,359 patients (98.8% follow-up) were available for analysis (93% American Society of Anesthesiologists class 1 to 2). The primary outcome occurred in 92.2% and 92.0%, corresponding to no motor function assessment being noninferior to motor function assessment with OR 0.97 (95% CI, 0.70 to 1.35). Adverse events in the ward during the first 24 h occurred in 5.8% versus 7.4% with or without motor function assessment, respectively (OR, 0.77; 95% CI, 0.5 to 1.19, P = 0.24).

Conclusions

PACU discharge without assessment of lower limb motor function after spinal anesthesia for total hip or knee arthroplasty was noninferior to motor function assessment in achieving length of stay 4 days or less or 30-day readmissions. Because a nonsignificant tendency toward increased adverse events during the first 24 h in the ward was discovered, further safety data are needed in patients without assessment of lower limb motor function before PACU discharge.
Janus kinase/signal transducer and activator of transcription pathways in spondyloarthritis
Authors: Raychaudhuri Smriti K. , Raychaudhuri Siba P.
Published: April 2017

Purpose of review

Cytokines are major drivers of autoimmunity, and biologic agents targeting cytokines have revolutionized the treatment of immune-mediated diseases. Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway represents a group of several intracellular molecules with a key role in signal pathways activated by growth factors and cytokines. These kinase proteins are associated with the signaling process of multiple key cytokines, which regulates various T-cell subpopulations and their effector cytokines. Development of novel drugs to inhibit this kinase cascade is an emerging field in clinical immunology. Thus, it is essential to have insights about the regulatory role of the JAK-STAT cytokine signaling in relation to autoimmune diseases and its applications in spondyloarthritis.

Recent findings

JAK-STAT kinase signaling proteins have been extensively studied in rheumatoid arthritis. Initial observations suggest that JAK-STAT kinase signaling cascade regulates activation and proliferation of the IL17+ effector memory T cells and thus has a potential role in the pathogenesis of psoriasis, psoriatic arthritis and ankylosing spondylitis.

Here, we provide an overview of the clinical rheumatologists about the significance of JAK-STAT signaling system in rheumatic diseases and introduce the potential application of JAK and STAT inhibitors in spondyloarthritis.
Risk factors, prevalence, and site concordance of human papillomavirus in high-risk Greek men
Authors: Tsikis Savas , Hoefer Lea , Bethimoutis George , Nicolaidou Electra , Paparizos Vassilios , Antoniou Christina , Chardalias Leonidas , Stavropoulos Georgios-Emmanouil , Sharma Shruti , Long Bradley C. , Mujacic Ibro , Kadri Sabah , Segal Jeremy P. , Furtado Larissa V. , Schneider John , Charnot-Katsikas Angella
Published: April 2017

The aim of this study was to determine the risk factors, genotype-specific prevalence, and concordance of human papillomavirus (HPV) infections at three anatomical sites in a cohort of high-risk Greek men. Patients were recruited from sexually transmitted infection and HIV clinics in Athens. Samples were obtained from oral, penile, and anal sites of 294 study participants and HPV testing was performed on 882 samples using next-generation sequencing. Patients also completed a questionnaire assessing risk factors for infection. The mean age of the participants was 33.1, 30% identified as men who have sex with men (MSM), and 21% were HIV positive. The prevalence of HPV was 49%; it was the highest at anal sites (33%) compared with 23% at penile sites (P=0.008) and 4% at oral sites (P<0.001). The most common HPV types in order of frequency were 6, 44, 16, 53, and 89. The genotype concordance rate was the highest between the penile and anal sites (7%), followed by 2% for anal–oral concordance. Identifying as MSM [adjusted odds ratios (aOR)=6.75, P<0.001] and being HIV positive (aOR=2.89, P=0.026) were significant risk factors for anal HPV infection, whereas alcohol use (aOR=0.45, P=0.002) was associated negatively with infection. The only significant risk factor for oral infection was an older age of sexual debut (aOR=1.32, P=0.038). Nearly half of our study participants tested positive in at least one of three anatomical sites. Using next-generation sequencing, we could identify high-risk types that are not covered by the current vaccine and would be missed by traditional HPV testing kits.
Sox10 and DOG1 Expression in Primary Adnexal Tumors of the Skin
Authors: Lezcano Cecilia , Ho Jonhan , Seethala Raja R.
Published: April 2017

Primary skin adnexal tumors can be challenging to classify and must be discerned from cutaneous adenocarcinoma metastases from various sites. We evaluated expression of Sox10 and DOG1 in normal cutaneous adnexa and in 194 primary skin adnexal tumors, and compared their performance in discriminating primary skin adnexal tumors from cutaneous metastatic adenocarcinomas with that of p40 and p63. In normal skin adnexa, we noted Sox10 expression in both the secretory and myoepithelial cells in eccrine glands, but only in myoepithelial cells in apocrine glands. DOG1 demonstrated canalicular expression in eccrine glands, and weak expression in myoepithelial cells of apocrine glands, germinative cells of sebaceous glands, and outer root sheath of follicular infundibulum. Sox10 was expressed in 100% of cylindromas and spiradenomas, and in variable frequency in other benign and malignant tumors of sweat glands. DOG1 was positive in most cylindromas (87.5%), in only 10.5% of spiradenomas, and was variably expressed in other benign and malignant tumors of sweat glands. All syringomas (n = 20) were negative for Sox10 and DOG1. One out of the 33 follicular neoplasms was positive for Sox10 and DOG1 (3%). All sebaceous neoplasms were negative for Sox10, and 28.1% of them were positive for DOG1. Sox10 was specific (91.9%) but not sensitive (28.4%) for primary skin origin, and was far less accurate (38.5%) than p63 or p40 (95.5% accuracy). Combining Sox10 with p63 or p40 showed only very minimal gain in accuracy (96%). DOG1 expression in tumors showed low sensitivity and specificity for skin adnexal origin.
Creation and Validation of a Photonumeric Scale to Assess Volume Deficiency in the Infraorbital Region
Authors: Niforos François , Liew Steven , Acquilla Raj , Ogilvie Patricia , Safa Marva , Signorini Massimo , Jones Derek , Hawthorn Jan , Collins Caroline , Kerson Graeme , Sithamparanathan Myooran ,   The AIRS Study Group
Published: April 2017

BACKGROUND

The eyes are particularly important aesthetic features of the face and revitalization of the infraorbital region has become a focus of aesthetic treatments. Published infraorbital scales to date have limitations in that they have been descriptive, subjective, or have used computer-generated images. Thus, there is an unmet need for a validated scale based on actual images.

OBJECTIVE

To develop a practical photonumeric scale that respects the complex anatomy and age-related changes occurring in the orbital area.

METHODS AND MATERIALS

The Allergan Infra-oRbital Scale (AIRS) was developed through a multistep process in collaboration with 16 physicians (plastic surgeons, dermatologists, and aesthetic physicians). Scale development involved both online photographs and live assessments of subjects. Interrater and intrarater reliability was assessed using intraclass correlation coefficients (ICCs).

RESULTS

The final AIRS showed intrarater and interrater ICCs of 0.78 to 0.86 and 0.91 to 0.98 for live validation and 0.76 to 0.82 and 0.86 to 0.91 for online validation, respectively, demonstrating robust validity.

CONCLUSION

The AIRS can be considered a photonumeric scale that accurately describes volume loss in the infraorbital region. It has been validated and is appropriate for use in research or for everyday clinical use for both live and photographic assessment.
Structure-Function Relationship Between the Bruch Membrane Opening-based Minimum Rim Width and Visual Field Defects in Advanced Glaucoma
Authors: Imamoglu Serhat , Celik Nimet Burcu , Sevim Mehmet S. , Pekel Gokhan , Ercalik Nimet Yesim , Turkseven Kumral Esra , Bardak Handan
Published: April 2017

Purpose:

To investigate the relationship between the Bruch membrane opening-minimum rim width (BMO-MRW) (global and temporal) parameters with spectral-domain optical coherence tomography (SD-OCT) and visual field (VF) sensitivity on the 10-2 test in patients with advanced glaucoma.

Materials and Methods:

This cross-sectional, observational study included a total of 33 eyes of 29 patients. To evaluate VF sensitivity, automated white-on-white perimetry was performed using a Humphrey field analyzer. The mean deviation (MD) and pattern SD values were used to characterize the degree of functional damage. BMO-MRW and peripapillary retinal nerve fiber layer thickness were obtained with SD-OCT. According to the Garway-Heath map and fovea and BMO axis, the 90 degrees temporal sector of the optic disc corresponding to the central VF was divided into upper and lower parts.

Results:

The upper and lower temporal BMO-MRW parameters showed stronger correlations with the MD parameters of their corresponding VFs when compared with both global and temporal MRW parameters. Global and temporal retinal nerve fiber layer thickness parameters were also correlated with global MD parameters.

Conclusions:

BMO-MRW measurements in the upper and lower parts of the 90 degrees temporal sector of the optic nerve head by SD-OCT and their corresponding VF sensitivity on the 10-2 test were found highly correlated. These BMO-MRW measurements could offer a means of predicting the status of visual hemifields in patients who are unable to undergo VF testing. Further longitudinal studies with larger series evaluating BMO-MRW parameters with SD-OCT are also needed to monitor progression in advanced glaucoma.
Use of the Postural Assessment Scale for Stroke Patients in Determining Acute Care Discharge Recommendations
Authors: Lesser Melissa , Borst Joseph , Dekerlegand Jennifer
Published: April 2017

Purpose/Hypothesis:

Acute care therapists face many barriers that limit the use of screening tools including time constraints and lack of measures appropriate for use in this setting. The Postural Assessment Scale for Stroke patients (PASS) was developed to assess sitting, lying, and standing balance in persons who experienced a stroke. The StrokEDGE taskforce highly recommends the PASS for acute care, as it has excellent psychometric properties and clinical utility. This project used the PASS and the modified Rankin Scale (mRS) to assess mobility in persons with an acute stroke. The purpose of this quality improvement project was to assess the feasibility of physical therapists' use of the PASS as a screening tool to assist with discharge recommendations.

Description:

Data were collected during a 6-month period from the neurology floor of a 782-bed acute care hospital. Persons admitted with an acute stroke and had received a therapy evaluation were included in the cohort. The goal was to assess the PASS during the initial evaluation within 48 hours of hospital admission. Concurrent data collected during this time included mRS scores, Functional Independence Measure (FIM) transfer and ambulation scores, and therapist discharge recommendations.

Results/Conclusions:

One hundred fifty-three subjects, with a mean age of 64.5 ± 15.5 years, were included in this cohort. The mean PASS score was 19.7 ± 11.1, the mean mRS score was 3.7 ± 2.2, and the mean FIM scores was 2.7 ± 2.4 for transfers and 3.7 ± 1.6 for ambulation. Of the persons discharged home (N = 40), mean PASS scores were 31.8 for those recommended for home physical therapy (N = 14), 32.6 for an outpatient therapy recommendation (N = 12), and 34.9 for those requiring no therapy at discharge (N = 14). The mean PASS scores for persons with an acute rehabilitation recommendation (N = 100) was higher than those recommended for a skilled nursing facility/subacute rehabilitation (N = 13), 15.7 as compared with 9.5, respectively. Using the Pearson correlation coefficient, the PASS had a strong correlation with the FIM transfers at r = 0.90 and ambulation at r = 0.86, with a strong negative correlation to the mRS at r =−0.77 (P < .001).

Clinical Relevance:

Acute care therapists should consider using the PASS to help guide clinical decision making and discharge recommendations for persons hospitalized with a stroke.
Achieving a Culture of Mobility: Implementation of a Mobility Aide Program to Increase Patient Mobilizations in an Acute Care Hospital
Authors: Coughenour E. T. , Salmans K. J. , Skoch A. D. , Starks L. L. , Sabus C.
Published: April 2017

Background and Purpose:

Mobilization of patients during inpatient hospitalization has been shown to be an important aspect of quality care that reduces risk for a number of complications. It is impractical and cost prohibitive for physical therapists (PTs) alone to provide all mobilization activities to hospitalized patients. Patient mobilization requires an interprofessional approach with all staff prioritizing patient activity. This descriptive research captures the productivity and patient effect of a patient mobilization program within an inpatient unit: Does the implementation of a mobility aide (MA) in an acute care hospital increase overall patient mobilizations? Does the use of an MA alleviate the workload of a PT to allow focus on skilled intervention and decreased frequency of visits?

Methods:

The MA's primary responsibility was to provide mobility interventions for patients under the direction of the PT in collaboration with nursing staff to improve frequency of mobilization and allow PTs to concentrate on skilled interventions. The PT and MA educated registered nurses and family members on mobility techniques for specific situations and promoted patient mobilization by nursing staff. The MA workload log, physical therapy orders, treatment frequency, and category of professional/caretaker who provided the intervention were recorded for 519 patients after the MA program implementation. This was compared to nursing unit-level, baseline mobilization metrics 1 week prior to MA program implementation. Physical therapist use measured as frequency of visits in the plan of care was compared to an equivalent time period prior to program implementation.

Results:

Since implementation of the MA program in this acute care hospital, there has been an observed 36% increase in patients walking on the unit as well as a 48% decrease in patients with no mobilizations. Trends in PT encounter frequency and increased PT referrals suggest that the PTs are able to focus on skilled intervention rather than general mobilization. The cost of implementing the MA program has been determined to be offset by a 10% increase in new PT referrals. While daily and twice a day visits by the PT decreased, the frequency of 1 to 3 visits per week increased suggesting increased breadth of PT services.

Conclusion:

Adding an MA to patients' plan of care may be a cost-effective method to optimize patient mobility in the acute care hospital setting. The addition of an MA to a medical/surgical unit produced positive outcomes in number of patient mobilizations and allowed improved use of the PT.
Evaluation of Cochlear Duct Length Computations Using Synchrotron Radiation Phase-Contrast Imaging
Authors: Koch Robert W. , Elfarnawany Mai , Zhu Ning , Ladak Hanif M. , Agrawal Sumit K.
Published: April 2017

Hypothesis:

Evaluation of cochlear duct length (CDL) using novel imaging techniques will help improve the accuracy of existing CDL equations.

Background:

Various relationships relating A value measured from a patient's computed tomography scan and CDL have been proposed to aid in preoperative electrode selection and frequency mapping.

Methods:

Ten cadaveric temporal bones were scanned using synchrotron radiation phase-contrast imaging. Reference CDL values were calculated by placing points representing the organ of Corti (OC), lateral wall (LW), and electrode location (I) on the synchrotron radiation phase-contrast imaging slices along the length of the cochlea. The CDL estimates from the existing three equations (OC, LW, I) in addition to two newly proposed equations (OC and LW) were compared with reference CDL values at each respective location.

Results:

When compared with reference CDL values, the new OC equation improved the CDL estimates from a 6.2% error to a 5.1% error while the new LW equation improved the CDL estimate error from 3.9 to 3.6%. Bland–Altman plots revealed both new equations increased similarity to reference values and brought more samples to within clinically significant ranges. Validation of the original electrode location equation to the reference values showed a 4.6% difference.

Conclusion:

The newly proposed equations for LW and OC provided an improvement over past equations for determining CDL from the A value by showing improved agreement with reference values. Therefore, these equations can provide quick and accurate preoperative estimates of CDL for improving customized frequency mapping.
Uterine Inflammatory Myofibroblastic Tumors Frequently Harbor ALK Fusions With IGFBP5 and THBS1
Authors: Haimes Josh D. , Stewart Colin J.R. , Kudlow Brian A. , Culver Brady P. , Meng Bo , Koay Eleanor , Whitehouse Ann , Cope Nichola , Lee Jen-Chieh , Ng Tony , McCluggage W. Glenn , Lee Cheng-Han
Published: April 2017

Inflammatory myofibroblastic tumor (IMT) can occur in a number of anatomic sites, including the uterus. Like its soft tissue counterpart, uterine IMT frequently expresses ALK and harbors ALK genetic rearrangements. The aim of this study is to fully characterize the genetic fusions that occur in uterine IMT. We studied 11 uterine IMTs with typical histology and 8 uterine myxoid smooth muscle tumors (5 leiomyomas, 1 smooth muscle tumor of uncertain malignant potential, and 2 leiomyosarcomas) in which the differential of IMT was considered, using a RNA-sequencing–based fusion assay to detect genetic fusions involving ALK, ROS1, RET, NTRK1/3, and other genes. ALK was expressed in 10 of 11 IMTs and 1 tumor initially categorized as a myxoid leiomyoma (granular cytoplasmic staining with paranuclear accentuation). Fusion transcripts involving ALK were identified in 9 of 10 ALK immunopositive IMTs, with 3 harboring IGFBP5-ALK, 3 harboring THBS1-ALK, 2 harboring FN1-ALK, and 1 harboring TIMP3-ALK. Among the smooth muscle tumors, IGFBP5-ALK fusion transcript was identified in only 1 ALK immunopositive case. Further review revealed that although a diagnosis of IMT was considered for the ALK immunopositive myxoid leiomyoma, this diagnosis was not initially rendered only because fluorescence in situ hybridization analysis was interpreted as negative for ALK genetic rearrangement; this case is best reclassified as an IMT. Notably, all the ALK fusions identified in our study included the transmembrane domain-encoding exon 19 of ALK. Our findings confirm the high frequency of ALK fusions in uterine IMT, with an enrichment of novel 5′ ALK fusion partners (IGFBP5, THBS1, and TIMP3) and exon 19-containing ALK fusion. Given that IGFBP5 and FN1 are both situated on the same chromosome as ALK, fluorescence in situ hybridization analysis for ALK rearrangement may not be reliable and a negative result should not exclude a diagnosis of uterine IMT if the histologic features and ALK immunostaining findings are supportive.
The North Carolina HIV Bridge Counselor Program: Outcomes From a Statewide Level Intervention to Link and Reengage HIV-Infected Persons in Care in the South
Authors: Seña Arlene C. , Donovan Jenna , Swygard Heidi , Clymore Jacquelyn , Mobley Victoria , Sullivan Kristen , LeViere Anna , Heine Amy , Quinlivan Evelyn B.
Published: April 2017

Background:

To improve the HIV continuum of care, a team of field service interventionists (State Bridge Counselors, SBC) was developed through a state public health system and provided brief (1–2) contacts for linkage of newly diagnosed persons with HIV and reengagement of persons living with HIV (PLWH) who were not in care.

Setting:

North Carolina, United States.

Methods:

Service data from January 2013 to June 2015 were analyzed to determine characteristics of clients referred to SBCs, proportions linked or reengaged in care, and/or achieved viral load suppression (VLs). We evaluated associations between client characteristics and outcomes using multivariable analyses and estimated odds ratios (OR) with 95% confidence intervals (CI).

Results:

SBCs provided linkage services to 299 newly diagnosed individuals and reengagement services to 606 PLWH throughout North Carolina. Among persons who received linkage services, 189 (63%) had evidence of care within 90 days of referral and 205 (69%) had VLs within a year. Among PLWH who received reengagement services, 278 (46%) had care within 90 days and 308 (51%) had VLs within a year. Persons aged 30–39 years (OR, 2.1; 95% CI, 1.1 to 3.9) and 40–49 years had an increased likelihood (OR, 2.4; 95% CI, 1.1 to 5.2) of linkage within 90 days compared with persons aged 18–29 years. Non-white PLWH had an increased OR of 1.7; (95% CI, 1.2 to 2.5) of reengagement compared with whites.

Conclusions:

Our SBC program successfully implemented a “low-touch” approach to provision of linkage and reengagement services, demonstrating that public health resources can be used to address the HIV care continuum on a statewide level.
Beyond Fidelity
Authors: Schoenherr Jordan Richard , Hamstra Stanley J.
Published: April 2017

Summary Statement

Fidelity has become a ubiquitous feature of discourse in simulation studies. Recent studies have highlighted the often ambiguous and contradictory manner in which fidelity has been defined, with each definition emphasizing different physical and functional features of simulation. We suggest that regarding fidelity as an objective property of a simulation obscures the interactive nature of the educator-learner relationship and should be abandoned. Rather than conceiving training as tasks performed by an individual in isolation, we suggest that it is more accurately understood as the social learning of affordances. Affordances represent the functional features of a simulator, which are taken as relevant in a specific learning context by means of analogy. Training is successful to the extent that educators and learners share an understanding of those affordances. Even when explicitly formulated, the concept of fidelity has greater difficulty accounting for the complex, interactional features of the training situation in comparison with accounts based on social learning. We conclude that continued attempts to redefine and use fidelity in the context of training will likely yield little benefit to the field compared with an interactive social learning framework.
Single Cardiac Ventricular Myosins Change Step-Size with Loading
Authors: Wang Yihua , Yuan Chen-Ching , Kazmierczak Katarzyna , Szczesna-Cordary Danuta , Burghardt Thomas P.
Published: April 2017

The cardiac myosin motor powers the beating heart by catalyzed ATPase free energy conversion to contractile work. Transgenic mouse models for heart disease express mouse α-cardiac myosin heavy chain with human essential light chain (ELC) in wild type (WT), or hypertrophic cardiomyopathy linked mutant forms, A57G or E143K. Mutants modify the ELC actin binding N-terminus or C-terminus regions. Motility and single myosin mechanical characteristics show stark contrasts between the motors related to their average force, power, and displacement while all indicate the ability to down-shift ensemble step-size with increasing load. A57G and E143K consume more ATP than control WT in the presence of actin with A57G upregulating and E143K downregulating power compared with WT. Higher ATP consumption and downregulated power in E143K implies a lower unitary force. Effects on power are consistent with an A57G that impairs the ELC N-terminus actin binding and an E143K that reduces lever-arm rigidity.
Establishment in Culture of Expanded Potential Stem Cells
Authors: Yang Jian , Ryan David J. , Wang Wei , Tsang Jason Cheuk-Ho , Lan Guocheng , Masaki Hideki , Gao Xuefei , Antunes Liliana , Yu Yong , Zhu Zhexin , Wang Juexuan , Kolodziejczyk Aleksandra A. , Campos Lia S. , Wang Cui , Yang Fengtang , Zhong Zhen , Fu Beiyuan , Eckersley-Maslin Melanie , Woods Michael , Tanaka Yosuke , Wilkinson Adam C. , Bussell James , White Jacqui , Ramirez-Solis Ramiro , Reik Wolf , Göttgens Berthold , Teichmann Sarah A. , Nakauchi Hiromitsu , Zou Xiangang , Lu Liming , Liu Pentao
Published: April 2017

Mouse embryonic stem cells are derived fromin vitroexplantation of blastocyst epiblasts1,2and contribute to both the somatic lineage and germline when returned to the blastocyst3but are normally excluded from the trophoblast lineage and primitive endoderm4–6. Here, we report that cultures of expanded potential stem cells (EPSCs) can be established from individual blastomeres, by direct conversion of mouse embryonic stem cells (ESCs) and by genetically reprogramming somatic cells. Remarkably, a single EPSC contributes to the embryo proper and placenta trophoblasts in chimeras. Critically, culturing EPSCs in a trophoblast stem cell (TSC) culture condition permits direct establishment of TSC lines without genetic modification. Molecular analyses including single cell RNA-seq reveal that EPSCs share cardinal pluripotency features with ESCs but have an enriched blastomere transcriptomic signature and a dynamic DNA methylome. These proof-of-concept results open up the possibility of establishing cultures of similar stem cells in other mammalian species.
Polygenic prediction of the phenome, across ancestry, in emerging adulthood
Authors: Docherty Anna R. , Moscati Arden , Dick Danielle , Savage Jeanne E. , Salvatore Jessica E. , Cooke Megan , Aliev Fazil , Moore Ashlee A. , Edwards Alexis C. , Riley Brien P. , Adkins Daniel E. , Peterson Roseann , Webb Bradley T. , Bacanu Silviu A. , Kendler Kenneth S.
Published: April 2017

Background

Identifying genetic relationships between complex traits in emerging adulthood can provide useful etiological insights into risk for psychopathology. College-age individuals are under-represented in genomic analyses thus far, and the majority of work has focused on clinical disorder or cognitive abilities rather than normal-range behavioral outcomes.

Methods

This study examined a sample of emerging adults 18-22 years of age (N = 5,947) to construct an atlas of polygenic risk for 33 traits predicting relevant phenotypic outcomes. Twenty-eight hypotheses were tested based on the previous literature on samples of European ancestry, and the availability of rich assessment data allowed for polygenic predictions across 55 psychological and medical phenotypes.

Results

Polygenic risk for schizophrenia in emerging adults predicted anxiety, depression, nicotine use, trauma, and family history of psychological disorders. Polygenic risk for neuroticism predicted anxiety, depression, phobia, panic, neuroticism, and was correlated with polygenic risk for cardiovascular disease.

Conclusions

These results demonstrate the extensive impact of genetic risk for schizophrenia, neuroticism, and major depression on a range of health outcomes in early adulthood. Minimal cross-ancestry replication of these phenomic patterns of polygenic influence underscores the need for more genome-wide association studies of non-European populations.
Response reversal during top-down modulation in cortical circuits with multiple interneuron types
Authors: del Molino Luis Carlos Garcia , Yang Guangyu Robert , Mejias Jorge F. , Wang Xiao-Jing
Published: April 2017

Pyramidal cells and interneurons expressing parvalbumin, somatostatin, or vasoactive intestinal peptide show cell type-specific connectivity patterns leading to a canonical microcircuit across cortex. Dissecting the dynamics of this microcircuit is essential to our understanding of the mammalian cortex. However, experiments recording from this circuit often report counterintuitive and seemingly contradictory findings. For example, the response of a V1 neural population to top-down behavioral modulation can reverse from positive to negative when the bottom-up thalamic input changes. We developed a theoretical framework to explain such response reversal, and we showed how this complex dynamics can emerge in circuits that possess two key features: the presence of multiple interneuron populations and a non-linear dependence between the input and output of the populations. Furthermore, we built a cortical circuit model and the comparison of our simulations with real data shows that our model reproduces the complex dynamics observed experimentally in mouse V1. Our explicit calculations allowed us to pinpoint the connections critical to response reversal, and to predict the existence of more types of complex dynamics that could be experimentally tested and the conditions to observe them.
Evolutionary compromises to environmental toxins: ammonia and urea tolerance inDrosophila suzukiiandDrosophila melanogaster
Authors: Belloni Virginia , Galeazzi Alessia , Bernini Giulia , Mandrioli Mauro , Versace Elisabetta , Haase Albrecht
Published: April 2017

The invasive speciesDrosophila suzukiihas evolved morphological and behavioral adaptations to lay eggs under the skin of fresh fruits. This results in severe damage of a wide range of small and stone fruits, thus making this species a serious agricultural and economical threat.

Drosophila suzukiifemales typically lay few eggs per fruit, preferring not infested fruits. Hence larvae are exposed to a reduced amount of nitrogenous waste products. On the contrary, the innocuousDrosophila melanogasterlays eggs on fermented fruits already infested by conspecifics, with larvae developing in a crowded environment characterized by accumulation of nitrogenous waste such as ammonia and urea. Given these differences in oviposition and larval ecological niche, we expected different behavioral and physiological mechanisms in the two species to cope with nitrogenous waste. We investigated the impact of different concentrations of ammonia and urea on fecundity and larval development in both species. Females and larvae ofD. suzukiishowed a greater sensitivity to high concentration of both compounds, with a dramatic decrease in fecundity and egg viability.

To better understand the pathways underlying these differences, we evaluated the effect on ornithine aminotransferase and glutathione-S-transferase, two enzymes involved in nitrogen metabolism and stress response that are expressed during larval development. Under ammonia and urea exposure, the expression of these enzymes was significantly reduced inD. suzukii.

The fact thatD. suzukii’s shift from rotten to fresh fruit as oviposition and larval substrate resulted in less efficient detoxifying and excretory mechanisms represents a potential approach for its control. Fecundity and larval development are in fact dramatically impaired by nitrogen waste products. These findings can help in planning effective strategies of sustainable pest management that targets both females and larvae.
Literature Evidence in Open Targets – a target validation platform
Authors: Kafkas Şenay , Dunham Ian , McEntyre Johanna
Published: April 2017

Background

We present the Europe PMC literature component of Open Targets – a target validation platform that integrates various evidence to aid drug target identification and validation. The component identifies target-disease associations in documents and ranks the documents based on their confidence from the Europe PMC literature database, by using rules utilising expert-provided heuristic information and serves the platform regularly with the up-to-date data since December, 2015.

Results

Currently, there are a total number of 1168365 distinct target-disease associations text mined from >26 million PubMed abstracts and >1.2 million Open Access full text articles. Our comparative analyses on the current available evidence data in the platform revealed that 850179 of these associations are exclusively identified by literature mining.

Conclusion

This component helps the platform’s users by providing the most relevant literature hits for a given target and disease. The text mining evidence along with the other types of evidence can be explored visually throughhttps://www.targetvalidation.organd all the evidence data is available for download in json format fromhttps://www.targetvalidation.org/downloads/data.
Sex differences in 20-hydroxyecdysone hormone levels control sexual dimorphism inBicyclus anynanabutterfly wing patterns
Authors: Bhardwaj S. , Prudic KL , Bear A. , Gupta MD , Wasik BR , Tong X. , Cheong WF , Wenk MR , Monteiro A.
Published: April 2017

In contrast to the important role of hormones in the development of sexual dimorphic traits in vertebrates [1], the differentiation of these traits in insects is attributed exclusively to variation in cell-autonomous mechanisms controlled by members of the sex determination pathway [2], such asdoublesex(dsx). Although hormones can shape the development of sexual traits in insects, and interact withdsxto create dimorphisms, variation in hormone levels are not known to cause dimorphism in these traits [3]. Here we show that butterflies use sex-specific differences in 20-hydroxyecdysone (20E) hormone titers to create sexually dimorphic wing ornaments, without the local involvement ofdsx. Females of the dry season (DS) form ofBicyclus anynanadisplay a larger sexual ornament on their wings than males, whereas in the wet season (WS) form both sexes have similarly sized ornaments [4]. High levels of circulating 20E during larval development in DS females and WS forms cause proliferation of the cells fated to give rise to this wing ornament, and results in sexual dimorphism in the DS forms. This study advances our understanding of how the environment regulates sex-specific patterns of plasticity of sexual ornaments and conclusively shows that sex-specific variation in hormone titers can play a role in the development of secondary sexual traits in insects, just like they do in vertebrates.

Highlights

Sex-specific levels of 20E, an insect molting hormone, regulate secondary sexual trait dimorphism and plasticity in butterflies.

20E levels above a threshold promote local patterns of cell division in one sex, but not in the other sex, to create sexually dimorphic eyespots.

eTOC

Sexual selection drives the evolution of ornaments for individuals to display to the opposite sex. Yet, the mechanisms by which sexual selection operates are still not well understood. Here Bhardwajet al. provide conclusive evidence, for the first time, that male and female insects use variation in levels of hormones to create dimorphism in their sexual ornaments. Authors show that 20-hydroxyecdyone, the insect molting hormone, also functions as a sex hormone in a butterfly. They also show how the environment shapes the development of sexual ornaments at a proximate level.
Four-sphere head model for EEG signals revisited
Authors: Næss Solveig , Chintaluri Chaitanya , Ness Torbjørn V. , Dale Anders M. , Einevoll Gaute T. , Wójcik Daniel K.
Published: April 2017

Electric potential recorded at the scalp (EEG) is dominated by contributions from current dipoles set by active neurons in the cortex. Estimation of these currents, called ’inverse modeling’, requires a ’forward’ model, which gives the potential when the positions, sizes, and directions of the current dipoles are known. Diﬀerent models of varying complexity and realism are used in the field. An important analytical example is thefour-sphere modelwhich assumes a four-layered spherical head where the layers represent brain tissue, cerebrospinal fluid (CSF), skull, and scalp, respectively. This model has been used extensively in the analysis of EEG recordings. Since it is analytical, it can also serve as a benchmark against which numerical schemes, such as the Finite Element Method (FEM), can be tested. While conceptually clear, the mathematical expression for the scalp potentials in the four-sphere model is quite cumbersome, and we observed the formulas presented in the literature to contain errors. We here derive and present the correct analytical formulas for future reference. They are compared with the results of FEM simulations of four-sphere model. We also provide scripts for computing EEG potentials in this model with the correct analytical formula and using FEM.
Sequence Alignment on Directed Graphs
Authors: Vaddadi Kavya , Sivadasan Naveen , Tayal Kshitij , Srinivasan Rajgopal
Published: April 2017

Genomic variations in a reference collection are naturally represented as genome variation graphs. Such graphs encode common subsequences as vertices and the variations are captured using additional vertices and directed edges. The resulting graphs are directed graphs possibly with cycles. Existing algorithms for aligning sequences on such graphs make use of partial order alignment (POA) techniques that work on directed acyclic graphs (DAG). For this, acyclic extensions of the input graphs are first constructed through expensive loop unrolling steps (DAGification). Also, such graph extensions could have considerable blow up in their size and in the worst case the blow up factor is proportional to the input sequence length. We provide a novel alignment algorithm V-ALIGN that aligns the input sequence directly on the input graph while avoiding such expensive DAGification steps. V-ALIGN is based on a novel dynamic programming formulation that allows gapped alignment directly on the input graph. It supports affine and linear gaps. We also propose refinements to V-ALIGN for better performance in practice. In this, the time to fill the DP table has linear dependence on the sizes of the sequence, the graph and its feedback vertex set. We perform experiments to compare against the POA based alignment. For aligning short sequences, standard approaches restrict the expensive gapped alignment to small filtered subgraphs having high ‘similarity’ to the input sequence. In such cases, the performance of V-ALIGN for gapped alignment on the filtered subgraph depends on the subgraph sizes.
Bayesian Inference of Species Networks from Multilocus Sequence Data
Authors: Zhang Chi , Ogilvie Huw A. , Drummond Alexei J. , Stadler Tanja
Published: April 2017

Reticulate species evolution, such as hybridization or introgression, is relatively common in nature. In the presence of reticulation, species relationships can be captured by a rooted phylogenetic network, and orthologous gene evolution can be modeled as bifurcating gene trees embedded in the species network. We present a Bayesian approach to jointly infer species networks and gene trees from multilocus sequence data. A novel birth-hybridization process is used as the prior for the species network, and we assume a multispecies network coalescent (MSNC) prior for the embedded gene trees. We verify the ability of our method to correctly sample from the posterior distribution, and thus to infer a species network, through simulations. To quantify the power of our method, we reanalyze two large datasets of genes from spruces and yeasts. For the three closely related spruces, we verify the previously suggested homoploid hybridization event in this clade; for the yeast data, we find extensive hybridization events. Our method is available within the BEAST 2 add-onSpeciesNetwork, and thus provides an extensible framework for Bayesian inference of reticulate evolution.
Transcription factor clusters regulate genes in eukaryotic cells
Authors: Wollman Adam J. M. , Shashkova Sviatlana , Hedlund Erik G. , Friemann Rosmarie , Hohmann Stefan , Leake Mark C.
Published: April 2017

Transcription is regulated through binding factors to gene promoters to activate or repress expression, however, the mechanisms by which factors find targets remain unclear. Using single-molecule fluorescence microscopy, we determinedin vivostoichiometry and spatiotemporal dynamics of a GFP tagged repressor, Mig1, from a paradigm signaling pathway ofSaccharomyces cerevisiae. We find the repressor operates in clusters, which upon extracellular signal detection, translocate from the cytoplasm, bind to nuclear targets and turnover. Simulations of Mig1 configuration within a 3D yeast genome model combined with a promoter-specific, fluorescent translation reporter confirmed clusters are the functional unit of gene regulation.In vitroand structural analysis on reconstituted Mig1 suggests that clusters are stabilized by depletion forces between intrinsically disordered sequences. We observed similar clusters of a co-regulatory activator from a different pathway, supporting a generalized cluster model for transcription factors that reduces promoter search times through intersegment transfer while stabilizing gene expression.