bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the Quality of Evidence Presented at Annual General Meetings: A 5-Year Retrospective Study
Authors: Zamir Nasim , Gholami Arian , Jajarmi Yasmin , Jackson Chornenki Nicholas L. , Patel Ameen , Dore Kelly L.
Published: April 2019

Introduction:

Health care professionals rely on annual general meetings (AGMs) to obtain up-to-date information and practice guidelines relevant to their specialty. The majority of such information at meetings is presented through abstract sessions. However, the quality of the evidence presented during such abstract sessions is unclear. Standardized measures were applied to assess the quality of evidence of abstracts presented at the Canadian Society of Nephrology AGM over a 5-year period.

Methods:

Two authors independently reviewed all CSN AGM abstracts presented from 2012 to 2016. Using a schema published in 2011 by the Oxford Centre for Evidence-Based Medicine (OCEBM), each abstract was subsequently ranked based on the quality of evidence. Schema categories ranged from level I, representing the highest evidence quality, to level V, representing the lowest. The number of authors and the authors' institution affiliations were also collected from the abstracts, where available, or if affiliations were unclear, an internet search of the author was performed.

Results:

Six hundred forty-two articles were screened. In total, 70% (n = 450) met the inclusion criteria. When assessed, 15% of articles were level I (highest quality), 17% level II, 53% level III, 12% level IV, and 3% level V (lowest quality). A Jonckheere–Terpstra test demonstrated a significant trend of increasing quality of evidence (P < .05) and collaboration (P < .005) over the 5-year study period. There was a significant correlation between level of evidence and collaboration across years reviewed in the study, rs(98) = −0.226, P < .001.

Discussion:

The results indicate a consistent increase in quality of evidence and collaborative submissions over time. To the authors' knowledge, this is the first assessment and analysis of AGM presentation quality within internal medicine and its subspecialties. Documenting and monitoring changes in the quality of evidence with a standardized framework may offer valuable insight pertaining to the medical field and the research community.
Ectopic Ocular Surface Calcification in Patients With Hypophosphatasia Treated With Asfotase Alfa
Authors: Gospe Sidney M. , Santiago-Turla Cecilia , DeArmey Stephanie M. , Cummings Thomas J. , Kishnani Priya S. , Bhatti M. Tariq
Published: April 2019

Purpose:

To assess for ectopic ocular calcification in a series of patients with hypophosphatasia (HPP) treated with asfotase alfa, a recombinant tissue-nonspecific alkaline phosphatase.

Methods:

This is a retrospective analysis of subjects enrolled at Duke University Medical Center in ENB-009-10 (ClinicalTrials.gov: NCT01163149), a randomized controlled trial of asfotase alfa in adolescents and adults with HPP. Seven patients between the ages of 45 and 66 years diagnosed with HPP based on clinical features and low serum alkaline phosphatase levels were enrolled at our site. Subjects were randomized to receive either daily subcutaneous injections of asfotase alfa or no treatment. After 24 weeks, during the open-label extension phase, all subjects received treatment for at least 4 years. All subjects underwent comprehensive eye examinations at baseline and at 24-week intervals throughout the study to assess for development of ocular calcifications.

Results:

By week 120, all 7 subjects developed asymptomatic white refractile deposits in the interpalpebral perilimbal conjunctiva. Biopsy of the conjunctival lesions in 2 subjects revealed elastosis with subepithelial calcification. The lesions were nonprogressive and in 5 subjects exhibited some degree of regression.

Conclusions:

Asfotase alfa was invariably associated with development of mild focal conjunctival calcification, likely through disinhibition of hydroxyapatite crystal propagation. The calcifications were not symptomatic or vision-threatening and should not preclude enzyme replacement therapy for patients with this rare and often debilitating disease.
Outcomes of Corneal Transplantation Using Donor Corneas Retrieved From Snakebite Victims
Authors: Donthineni Pragnya Rao , Chaurasia Sunita , Garg Prashant
Published: April 2019

Purpose:

To report the outcomes of corneal transplantation using donor corneas retrieved from snakebite victims.

Methods:

This study was a retrospective analysis of 30 corneal transplants performed from 2014 to 2016 using donor corneas retrieved from snakebite victims. The details of the donor corneal characteristics and the transplant recipients were collected from the eye bank and the medical records department.

Results:

The mean age of the donors was 30.4 ± 17.5 years. The median death-to-preservation time was 3.3 hours [interquartile range: 1.3–5.6 hours]. Ninety percent (27/30) of the corneas were evaluated as optical grade, and 10% (3/30) of the corneas were deemed as therapeutic grade. The mean endothelial cell density on specular microscopy of the donor corneas was 2943 ± 615 cells/mm2, and median corneal thickness was 514 μm (interquartile range: 506–520). Seventy-five percent of the corneas transplanted had cleared, with a mean follow-up duration of 1.5 ± 1.0 years (range: 0.4–3.7) years and mean logarithm of the minimum angle of resolution (LogMAR) visual acuity of 0.51 ± 0.27 (range: 0–1.2) at the last follow-up.

Conclusions:

The donor corneas retrieved from snakebite victims are apparently safe and suitable for transplantation, and screening for such donor corneas should include a thorough examination of ocular adnexa to rule out local envenomation before corneal retrieval in addition to the routine evaluation protocol.
Three-Year Outcome Comparison Between Femtosecond Laser-Assisted and Manual Descemet Membrane Endothelial Keratoplasty
Authors: Sorkin Nir , Mednick Zale , Einan-Lifshitz Adi , Trinh Tanya , Santaella Gisella , Telli Alexandre , Chan Clara C. , Rootman David S.
Published: April 2019

Purpose:

To evaluate 3-year outcomes of femtosecond laser-assisted Descemet membrane endothelial keratoplasty (F-DMEK) compared with manual Descemet membrane endothelial keratoplasty (M-DMEK) in patients with Fuchs endothelial corneal dystrophy (FECD).

Methods:

A retrospective, interventional study, including eyes with FECD and cataract that underwent either F-DMEK or M-DMEK combined with cataract extraction at either the Toronto Western Hospital or Kensington Eye Institute, and that had at least 18 months' follow-up was conducted. Exclusion criteria: complicated anterior segments, previous vitrectomy, previous keratoplasty, corneal opacity, or any other visually significant ocular comorbidity.

Results:

Included were 16 eyes of 15 patients in the F-DMEK group (average follow-up 33.0 ± 9.0 months) and 45 eyes of 40 patients in the M-DMEK group (average follow-up 32.0 ± 7.0 months). There were no issues with the creation of femtosecond descemetorhexis (in the F-DMEK group)—all descemetorhexis cuts were complete. Best spectacle-corrected visual acuity improvement did not differ significantly between the groups at 1, 2, and 3 years (P = 0.849, P = 0.465 and P = 0.936, respectively). Rates of significant detachment in F-DMEK and M-DMEK were 1 of 16 eyes (6.25%) and 16 of 45 eyes (35.6%) (P = 0.027). Rebubbling rates were 1 of 16 eyes (6.25%) and 15 of 45 eyes (33.3%) (P = 0.047). Cell-loss rates following F-DMEK and M-DMEK were 26.8% and 36.5% at 1 year (P = 0.042), 30.5% and 42.3% at 2 years (P = 0.008), 37% and 47.5% at 3 years (P = 0.057), respectively. Graft failure rate was 0% in F-DMEK and 8.9% in M-DMEK (all were primary failures; P = 0.565).

Conclusions:

F-DMEK showed good efficacy with reduced detachment, rebubble, and cell-loss rates, compared with M-DMEK.
Concussion Symptoms Predictive of Adolescent Sport-Related Concussion Injury
Authors: Harriss Alexandra B. , Abbott Kolten C. , Humphreys David , Daley Mark , Moir Marci Erin , Woehrle Emilie , Balestrini Christopher S. , Fischer Lisa K. , Fraser Douglas D. , Shoemaker Joel Kevin
Published: April 2019

Objective:

To assess the predictive capability of the postconcussion symptom scale (PCSS) of the sport concussion assessment tool (SCAT) III to differentiate concussed and nonconcussed adolescents.

Design:

Retrospective.

Setting:

Tertiary.

Participants:

Sixty-nine concussed (15.2 ± 1.6 years old) and 55 control (14.4 ± 1.7 years old) adolescents.

Independent Variables:

Postconcussion symptom scale.

Main Outcome Measure:

Two-proportion z-test determined differences in symptom endorsement between groups. To assess the predictive power of the PCSS, we trained an ensemble classifier composed of a forest of 1000 decision trees to classify subjects as concussed, or not concussed, based on PCSS responses. The initial classifier was trained on all 22-concussion symptoms addressed in the PCSS, whereas the second classifier removed concussion symptoms that were not statistically significant between groups.

Results:

Concussion symptoms common between groups were trouble falling asleep, more emotional, irritability, sadness, and anxious. After removal, analysis of the second classifier indicated that the 5 leading feature rankings of symptoms were headache, head pressure, light sensitivity, noise sensitivity, and “don't feel right,” which accounted for 52% of the variance between groups.

Conclusions:

Collectively, self-reported symptoms through the PCSS can differentiate concussed and nonconcussed adolescents. However, predictability for adolescent patients may be improved by removing emotional and sleep domain symptoms.
Delayed-Union of Acetabular Stress Fracture in Female Gymnast: Use of Teriparatide to Augment Healing
Authors: Gende Alecia , Thomsen Timothy W. , Marcussen Britt , Hettrich Carolyn
Published: April 2019

Pelvic stress fractures are rare and present unique challenges for medical personnel. Delayed healing can lead to increased physical, psychological, and social stress for athletes. Recent literature suggests effective use of a synthetic derivative of parathyroid hormone, teriparatide, to augment healing of delayed-union stress fractures. We present a case of a female National Collegiate Athletic Association Division I gymnast successfully returned to play after a 12-week course of teriparatide injections for an ischioacetabular stress fracture.
Multimodal Assessment of Sport-Related Concussion
Authors: Sherry Natalie Sandel , Fazio-Sumrok Vanessa , Sufrinko Alicia , Collins Michael W. , Kontos Anthony P.
Published: April 2019

Objective:

The purpose of this study was to determine which assessments best identify athletes with sport-related concussion (SRC) from healthy controls in the acute/early subacute phase (within 10 days of SRC) of injury.

Design:

Prospective, cohort study.

Setting:

Specialty concussion clinic.

Participants:

Sixty-four athletes with SRC (52% male) and 59 matched (age and sex), healthy controls (56% male) aged 12 to 20 years (Mean [M] = 15.07, Standard Deviation [SD] = 2.23).

Assessment:

Participants completed symptom, cognitive, vestibular/oculomotor, near point of convergence (NPC), and balance assessments.

Main Outcome Measures:

Univariate analyses were conducted to compare athletes with SRC to healthy controls across all assessments. Assessments that significantly differed between the SRC group and healthy controls were used as predictors in an enter method logistic regression (LR) model and subsequent forward stepwise LR.

Results:

Results of LR analyses indicated that symptom inventory and symptom provocation on vestibular/oculomotor assessments significantly predicted athletes with SRC versus controls. The forward stepwise LR accurately classified 84.6% of the overall sample (78.3% of athletes with SRC and 91.2% of controls were accurately predicted) and accounted for 60.5% of the variance in predicting athletes with SRC versus controls. Total symptom inventory score (P = 0.003) and vestibular/oculomotor symptom provocation (P < 0.01) were the most sensitive and specific measures in a comprehensive, multimodal assessment for distinguishing athletes with SRC from healthy controls within 10 days of injury.

Conclusions:

Elements within a multimodal evaluation that are the most robust at discriminating athletes with SRC from healthy controls in the acute/early subacute phase of injury include symptom report and provocation of symptoms on vestibular/oculomotor assessment. These assessments should be considered in conjunction with other objective assessments (ie, NPC measurement and cognitive testing) as part of a comprehensive evaluation of SRC.
Therapeutic Benefit of Blood Transfusion in a Patient With Novel PGK1 Mutation (c.461T>C [p.L154P])
Authors: Ward Scott K. , Stevens Cathy A. , Keates-Baleeiro Jennifer , Bhakta Manoo
Published: April 2019

Phosphoglycerate kinase (PGK) is glycolytic enzyme critical in the creation of adenosine triphosphate. Mutations in the gene for this enzyme, PGK1, are associated with PGK deficiency, which is characterized by neurologic symptoms, nonhereditary spherocytic hemolytic anemia, and myopathy. We present a 20-year-old male with a novel c.461T>C (p.L154P) PGK1 mutation and clinical disease complicated by anemia and neurological symptoms. There is no recommended treatment for PGK deficiency. Because of our patient’s advanced disease progression, we initiated serial blood transfusions and report significant subjective improvement in the patient’s physical condition before his passing from PGK deficiency-related complications.
A Pediatric Case of Transformed Mycosis Fungoides in a BRCA2 Positive Patient
Authors: Gross Andrea M. , Turner Joyce , Kirkorian Anna Y. , Okoye Ginette A. , Luca Dragos C. , Bornhorst Miriam , Jacobs Shana S. , Williams Kirsten M. , Schore Reuven J.
Published: April 2019

Cutaneous T-cell lymphomas are very rare in children. Although mycosis fungoides is the most common of these rare cutaneous T-cell lymphomas in children, transformation to an aggressive malignancy remains extremely uncommon, and there are no clear guidelines for clinical management in the pediatric population. In addition, the increased usage of next-generation sequencing for pediatric patients with unusual malignancies may result in the discovery of pathogenic germline mutations, though the association between these mutations and the patient’s cancer is not always clear. We present here a unique pediatric case of transformed mycosis fungoides in a patient with BRCA2 mutation.
Organ Weight Reference Ranges for Ages 0 to 12 Years
Authors: Molina D. Kimberley , Pinneri Kathy , Stash John A. , Li Ling , Vance Kathryn , Cross Caroline
Published: April 2019

Abnormal organ weights often serve as an indicator of underlying disease or other pathological process making assessment of organ weight a critical part of the autopsy examination and interpretation. Unfortunately, normal organ weights for children are often based on studies done in the 1930s and 1960s. Thus, the present study was designed to accurately assess organ weights in children to establish reference ranges for use in autopsy examinations. A total of 1759 traumatic deaths in children aged 0 to 12 years were reviewed. Analysis revealed that body length was the best predictor for organ weight. Reference ranges were established and stratified by both age and body length.
Papular Mycosis Fungoides Is a Distinctive Variant of Early-stage Mycosis Fungoides
Authors: Saggini Andrea , Fink-Puches Regina , Cota Carlo , Lora Viviana , Potzinger Heide , Massone Cesare , Cerroni Lorenzo
Published: April 2019

Papular mycosis fungoides (PMF) is a rare variant of mycosis fungoides (MF). The exact nosology and prognosis of PMF are still unclear. We retrospectively identified cases of PMF from the files of the Department of Dermatology of the Medical University of Graz, Austria, and checked the follow-up data. The patients comprised 13 men and 5 women (median age: 57.5 y; range 13 to 77 y). In 4 patients, an initial clinicopathologic diagnosis of atypical pityriasis lichenoides was made; these cases were subsequently reclassified as PMF due to the onset of conventional patches of MF during follow-up. Follow-up data of our cases showed that 2 patients died of disease progression 50 and 199 months after the first presentation, respectively. Two patients are alive with progressive disease after 215 and 300 months, respectively. Ten patients are alive with stable disease (median: 70 mo). Four patients were in complete remission at last follow-up visit (median: 215 mo; 2 of them died of unrelated causes). Our data confirm that PMF represents a clinicopathologic variant of early MF with prognosis similar to conventional presentations of the disease. Familiarity with PMF and distinction from other cutaneous papular lymphoid proliferations is necessary for a precise diagnosis and management of these patients.
Health Literacy, Self-management Activities, and Glycemic Control Among Adults With Type 2 Diabetes: A Path Analysis
Authors: Luo Huabin , Patil Shivajirao P. , Cummings Doyle M. , Bell Ronny A. , Wu Qiang , Adams Alyssa D.
Published: April 2019

Purpose:

This study evaluated a novel composite measure of health literacy and numeracy by assessing its predictive validity for diabetes self-care activities and glycemic control.

Methods:

Patients (N = 102) with type 2 diabetes were recruited from a family medicine clinic at an academic medical center. Combined health literacy was assessed by combining the results of the Health Literacy Scale and the Subjective Numeracy Scale. Self-management activities were assessed by the Summary of Diabetes Self-Care Activities scale. Hemoglobin A1c (A1c) values were extracted from patients' medical records to assess glycemic control. Path models were used to test the predicted pathways linking health literacy and numeracy, independently and together, to self-management activities and glycemic control.

Results:

The mean combined literacy score was 72.0 (range, 33-104); the mean health literacy score alone was 43.9 (range, 14-56); and the mean numeracy score alone was 28.1 (range, 8-48). The direct effects results showed that the combined health literacy score (B = 0.107, P < .05) and the health literacy score alone (B = 0.234, P < .05) were significantly associated with self-care activities. The health literacy score alone also had a significant direct effect on A1c (B = −0.081, P < .05). The indirect effects of the combined health literacy on glycemic control through self-care activities were not statistically significant.

Conclusions:

Findings from this study suggest that the combined health literacy has predictive validity for self-care activities whereas the health literacy alone has predictive validity for glycemic control. More research is needed to validate these findings. Higher patient health literacy skills were not consistently associated with higher perceived numeracy skills. Additional attention and efforts should be made to make sure patients understand medical instructions involving numerical calculations.
Building Collective Efficacy to Support Public Health Workforce Development
Authors: Tower Craig , Van Nostrand Elizabeth , Misra Ranjita , Barnett Daniel J.
Published: April 2019

Context:

Leaders in public health have made great advances in workforce development over the past 30 years, while shifting from an emphasis based in training on individual, technical skills to a more holistic development approach, which boosts crosscutting skills. Efforts to increase public health workforce capabilities remain focused on workers as individuals, rather than the workforce as a collective unit.

Program:

Research has shown that a strategic adult learning approach can improve both individual capabilities and the collective performance of the workforce, which can be explained using social cognitive theory and the concept of collective efficacy, or the collective belief of workers in the ability of the group to succeed. We explain how a prior training program pushed us to explore this approach.

Implementation:

The proposed approach covers proposed implementation strategies to build collective efficacy as part of existing workforce development initiatives, with a focus on 5 key steps.

Evaluation:

Experience in fields as diverse as sports psychology and organizational development has shown that it is possible to evaluate changes in collective efficacy using measures that can be adopted in public health.

Discussion:

Adjusting existing public health workforce development initiatives to build collective efficacy can help link workforce self-confidence to performance. More actionable data are needed to determine the best methods for achieving those goals in the field of public health.
Regional After-Action Review Among Local Health Department Personnel After Hurricane Matthew in Eastern North Carolina, United States
Authors: Lea C. Suzanne , Beasley Cherry M. , Cox Adrian
Published: April 2019

Hurricane Matthew impacted eastern North Carolina during October 2016. A regional after-action exercise was conducted as a moderated discussion using an adaptation of Federal Emergency Management Agency's (FEMA's) after-action report format to allow health departments to communicate lessons learned across jurisdictional lines. Forty-one professionals from 18 counties participated in a 2-hour workshop. Information on strengths, weaknesses, and recommendations was collected in small-group format, organized into county clusters by hazard mitigation regions and by 3 professional roles (health director, nursing director, and preparedness coordinator). Interagency agreements varied by county, depending on regularity of hurricanes and flooding. Improvement opportunities included enhanced coordination with American Red Cross in shelter operations and opening more special medical needs shelters. Participants emphasized successful coordination with county emergency management leaders. A regional after-action exercise designed as a moderated workshop focusing on the public health response provided an opportunity to exchange strengths and lessons learned after Hurricane Matthew in eastern North Carolina. This after-action approach may be useful for similar local health jurisdictions to build regional consensus for future disaster response planning and training.
Spatiotemporal Analysis of Oklahoma Tobacco Helpline Registrations Using Geoimputation and Joinpoint Analysis
Authors: Dilekli Naci , Janitz Amanda , Martinez Sydney , Gopalani Sameer , Dougherty Tyler , Williams Aaron , Sabzi Hamed Zamani , Campbell Janis
Published: April 2019

Objective:

Tobacco quitlines provide free smoking cessation telephone services to smokers interested in quitting tobacco. We aimed to explore spatial and temporal analyses of registrations to the Oklahoma Tobacco Helpline including those of any racial group and American Indians (AI) from January 1, 2006, to June 30, 2017. This will allow tribal and community organizations, such as the Oklahoma Tribal Epidemiology Center, to better implement and evaluate public health prevention efforts at a smaller geographic area using the larger geographic units that are publicly available.

Design:

Retrospective, descriptive study.

Setting:

Oklahoma.

Participants:

Registrants to the Oklahoma Tobacco Helpline.

Main Outcome Measures:

To evaluate the spatial distribution of Helpline participants using geoimputation methods and evaluate the presence of time trends measured through annual percent change (APC).

Results:

We observed increased density of participants in the major population centers, Oklahoma City and Tulsa. Density of AI registrations was higher in the rural areas of Oklahoma where there is a larger tribal presence compared with participants of any racial group. For all racial groups combined, we identified 3 significant trends increasing from July 2008 to March 2009 (APC: 10.9, 95% confidence interval [CI], 0.8-21.9), decreasing from March 2009 to May 2014 (APC: −0.8, 95% CI: −1.1 to −0.4), and increasing from May 2014 to June 2017 (APC: 0.8, 95% CI: 0.0-1.6). The number of AI registrations to the Helpline increased significantly from July 2008 to March 2009 (APC: 12.0, 95% CI: 2.0-22.9) and decreased from March 2009 to June 2014 (APC: −0.7, 95% CI: −1.0 to −0.3).

Conclusions:

Results of this project will allow the Helpline to efficiently identify geographic areas to increase registrations and reduce commercial tobacco use among the AI population in Oklahoma through existing programs at the Oklahoma Tribal Epidemiology Center.
An Observational Study of a Simulation-Based Cross-Discipline Learning Activity Between Theater Arts and Physical Therapy Students
Authors: Dennis Diane M. , Parry Sharon , Miolin Philip , Mercer Leah , Furness Anne
Published: April 2019

Introduction

Professional actors are often used to portray simulated patients during healthcare professional training. This study aimed to create an activity where physical therapy (PT) and theater arts (TA) students could address discrete learning outcomes in a common setting with mutual benefit.

Methods

Mixed methods observational study of 246 university students (201 PT, 45 TA) undertaking a scenario involving the provision of a clinical history. All students completed a 5-question qualitative survey relating to the activity, and each group scored themselves and each other using an observer rubric rating performance from 1 (do not agree) to 10 (agree).

Results

For PT students, the range of means (SDs) across the five questions were significantly different (P < 0.001) with 6.2 (1.6) to 6.8 (1.4) for self-assessment and 8.2 (1.4) to 8.7 (1.1) for TA assessment of PT. For TA students, across all repetitions and all questions, the mean (SD) was 7.6 (1.5) for self-assessment and 7.9 (1.2) for PT assessment of TA, representing a significant difference (P < 0.001). After initial enactment, there was a significant improvement in TA self-assessment of performance (P = 0.002), but thereafter, there was no significant difference over time (P = 0.114).

Qualitative data analysis revealed the following three themes common to both groups: worthiness, authenticity/realism, and anxiety/confidence. The PT students also identified history-taking skills and the importance of patient/PT relationships. The TA students identified learning around character portrayal, improvisation, and concentration.

Conclusions

This study describes a simulation-based learning activity undertaken within existing infrastructure with complementary learning objectives for both TA and PT students that was realistic and engaging.
Association of the Number of a Simulation Faculty With the Implementation of Simulation-Based Education
Authors: Takahashi Jin , Shiga Takashi , Funakoshi Hiraku , Homma Yosuke , Mizobe Michiko , Ishigami Yuichiro , Honda Hideki
Published: April 2019

Introduction

Although the implementation of simulation-based education (SBE) is essential for emergency medicine residency programs (EMRPs), little is known about the factors associated with its degree of SBE implementation in EMRPs. Therefore, this study aimed to investigate factors associated with SBE implementation in EMRPs. We hypothesized that the number of the simulation faculty was associated with the degree of SBE implementation.

Methods

We conducted a multicenter, cross-sectional survey on SBE implementation in emergency medicine resident education, in accredited EMRPs in the Greater Tokyo area, Japan. Survey question themes included institutional characteristics and the status of simulation education in them. For analyzing factors associated with SBE implementation, we defined EMRPs with a robust SBE implementation as those having an annual simulation time exceeding 10 hours.

Results

The survey response rate was 73% (115/158). Of the EMRPs that responded, 32% reported that their annual simulation time was more than 10 hours. In the unadjusted analysis, possession of a simulator in the emergency department was significantly associated with nonrobust SBE implementation, but the number of the simulation faculty was significantly associated. On adjusting for possession of a simulator in the emergency department, presence of simulation curriculum, and presence of simulation-based formative or comprehensive assessment, we observed an association of robust SBE implementation with a number of the simulation faculty (unit odds ratio = 1.33; 95% confidence interval = 1.10–1.60).

Conclusions

To our knowledge, this is the first Japanese study to demonstrate that the number of the simulation faculty at a program is independently associated with a robust SBE implementation.
Breast Cancer Detection
Authors: Veitch Daisy E. , Bochner Melissa , Molenbroek Johan F. M. , Goossens Richard H. M. , Owen Harry
Published: April 2019

Introduction

There is still a need for competent breast lump detection palpation skills, especially in developing countries. Our goal is to design, develop, and establish a test to determine whether students can, by touch alone, identify and discriminate between a range of different simulated lesions at different adiposity levels.

Methods

Common lesions, breast cancers, and cysts were physically simulated and hidden in a test object referred to as the “tactile landscape” (TL). Ribs, intercostal muscle, and nodularity—normal anatomical features—increased their realistic complexity. Varying depths of features simulated varying degrees of adiposity. A testing protocol was created to determine the testee's ability to identify and discriminate different commonly occurring breast masses using palpation. Five experts (four breast surgeons and one general practitioner) and 20 inexperienced medical students were recruited and tested. Results were compared.

Results

The TL has been based on previously verified breast models and has softness similar to 53% of women's breasts and nodularity similar to 60% as assessed in a breast clinic by breast surgeons. The five experts indicated that the simulated lesions felt like those they might encounter in clinical practice and all of them identified the lesions and nonlesions hidden in the TL 100% correctly, thus indicating the value of the model. In contrast, only one student was able to identify all the lesions. One student identified none of them. The remaining students mean score was 65%.

Conclusions

All students but one performed poorly in comparison to the experts. This indicates that the test could be useful to test students' ability to identify and discriminate breast masses. If successful, it will add previously missing capability to the mix of assessment instruments already used, thus potentially improving clinical breast examination training and assessment.
Widespread FUS mislocalization is a molecular hallmark of ALS
Authors: Tyzack Giulia E. , Luisier Raphaelle , Taha Doaa M. , Neeves Jacob , Modic Miha , Mitchell Jamie S. , Meyer Ione , Greensmith Linda , Newcombe Jia , Ule Jernej , Luscombe Nicholas M. , Patani Rickie
Published: April 2019

Amyotrophic lateral sclerosis (ALS)-causing mutations clearly implicate ubiquitously expressed and predominantly nuclear RNA binding proteins (RBPs), which form pathological cytoplasmic inclusions in this context. However, the possibility that wild-type RBPs mislocalize without necessarily becoming constituents of ALS cytoplasmic inclusions themselves remains unexplored. We hypothesized that nuclear-to-cytoplasmic mislocalization of the RBP Fused in Sarcoma (FUS), in an unaggregated state, may occur more widely in ALS that previously recognized. To address this hypothesis, we analysed motor neurons (MNs) from an human ALS induced-pluripotent stem cells (iPSC) model caused by the VCP mutation. Additionally, we examined mouse transgenic models and post-mortem tissue from human sporadic ALS cases. We report nuclear-to-cytoplasmic mislocalization of FUS in both VCP-mutation related ALS and, crucially, in sporadic ALS spinal cord tissue from multiple cases. Furthermore, we provide evidence that FUS protein binds to an aberrantly retained intron within the SFPQ transcript, which is exported from the nucleus into the cytoplasm. Collectively, these data support a model for ALS pathogenesis whereby aberrant intron-retention in SFPQ transcripts contributes to FUS mislocalization through their direct interaction and nuclear export. In summary, we report widespread mislocalization of the FUS protein in ALS and propose a putative underlying mechanism for this process.
Impaired speed encoding is associated with reduced grid cell periodicity in a mouse model of tauopathy
Authors: Ridler Thomas , Witton Jonathan , Phillips Keith G. , Randall Andrew D. , Brown Jonathan T.
Published: April 2019

Dementia is associated with severe spatial memory deficits which arise from dysfunction in hippocampal and parahippocampal circuits. For spatially-sensitive neurons, such as grid cells, to faithfully represent the environment these circuits require precise encoding of direction and velocity information. Here we have probed the firing rate coding properties of neurons in medial entorhinal cortex (MEC) in a mouse model of tauopathy. We find that grid cell firing patterns are largely absent in rTg4510 mice, while head direction tuning remains largely intact. Conversely, neural representation of running speed information was significantly disturbed, with smaller proportions of MEC cells having firing rates correlated with locomotion in rTg4510 mice. Additionally, the power of local field potential oscillations in the theta and gamma frequency bands, which in wildtype mice are tightly linked to running speed, was invariant in rTg4510 mice. These deficits in locomotor speed encoding likely severely impact path integration systems in dementia.
Correlation of Microglial Activation with White Matter Changes in Dementia with Lewy Bodies
Authors: Nicastro Nicolas , Mak Elijah , Williams Guy B. , Surendranathan Ajenthan , Bevan-Jones William Richard , Passamonti Luca , Rodriguez Patricia Vazquez , Su Li , Arnold Robert , Aigbirhio Franklin I. , Rowe James B. , O’brien John T.
Published: April 2019

Dementia with Lewy bodies (DLB) is the second-leading degenerative dementia after Alzheimer’s disase. Neuropathologically, it is characterized by alpha-synuclein protein deposition with variable degree of concurrent Alzheimer pathology. Neuroinflammation is increasingly recognized as a significant contributor of degeneration.

Objective

to examine the relationship between microglial activation as measured with [11C]-PK11195 brain PET and MR diffusion tensor imaging (DTI) in DLB.

Methods

nineteen clinically probable DLB and 20 similarly aged controls underwent structural MRI with T1-weighted and 3T DTI sequences. Eighteen DLB subjects also underwent [11C]-PK11195 PET imaging. Tract-Based Spatial Statistics (TBSS) were performed to compare DTI parameters in DLB relative to controls and identify associations of [11C]-PK11195 binding with white matter integrity.

Results

TBSS showed widespread changes in all DTI parameters in the DLB group compared to controls (Threshold Free Cluster Enhancement (TFCE) p < 0.05). [11C]-PK11195 binding in parietal cortices also correlated with widespread lower mean and radial diffusivity (TFCE p < 0.05).

Conclusion

Our study demonstrates that higher PK11195 binding is associated with a relative preservation of white matter, positioning neuroinflammation as a potential early marker in the DLB pathogenic cascade.
Using balances to engineer features for the classification of health biomarkers: a new approach to balance selection
Authors: Quinn Thomas P. , Erb Ionas
Published: April 2019

Since the turn of the century, technological advances have made it possible to obtain a molecular profile of any tissue in a cost-effective manner. Among these advances include sophisticated high-throughput assays that measure the relative abundance of microorganisms, RNA molecules, and metabolites. While these data are most often collected to gain new insights into biological systems, they can also be used as biomarkers to create clinically useful diagnostic classifiers. How best to classify high-dimensional “-omics” data remains an area of active research. However, few explicitly model the relative nature of these data, and instead rely on cumbersome normalizations which often invoke untestable assumptions. This report (a) emphasizes the relative nature of health biomarkers, (b) discusses the literature surrounding the classification of relative data, and (c) benchmarks how different transformations perform across multiple biomarker types. In doing so, this report explores how one could use balances to engineer features prior to classification, and proposes a simple procedure, called discriminative balance analysis, to select discriminative 2- and 3-part balances.
Divergent neural pathways emanating from the lateral parabrachial nucleus mediate distinct components of the pain response
Authors: Chiang Michael C. , Nguyen Eileen K. , Papale Andrew E. , Ross Sarah E.
Published: April 2019

The lateral parabrachial nucleus (lPBN) is a major target of spinal projection neurons conveying nociceptive input into supraspinal structures. However, the functional role of distinct lPBN efferents for diverse nocifensive responses have remained largely uncharacterized. Here, we show that two populations of efferent neurons from different regions of the lPBN collateralize to distinct targets. Activation of efferent projections to the ventromedial hypothalamus (VMH) or lateral periaqueductal gray (lPAG) drive escape behaviors, whereas the activation of lPBN efferents to the bed nucleus stria terminalis (BNST) or central amygdala (CEA) generates an aversive memory. Finally, we provide evidence that dynorphin expressing neurons span cytoarchitecturally distinct domains of the lPBN to coordinate these distinct aspects of the nocifensive response.

HIGHLIGHTS

Spatially segregated neurons in the lPBN collateralize to distinct targets.

Distinct output pathways give rise to separate aspects of the pain response.

Dynorphin neurons within the lPBN convey noxious information across subdivisions.

eTOC BLURB

Chiang et al. reveal that neurons in spatially segregated regions of the lateral parabrachial nucleus collateralize to distinct targets, and that activation of distinct efferents gives rise to separate components of the nocifensive response.
Cell adhesion molecule interaction with Piezo1 channels is a mechanism for sub cellular regulation of mechanical sensitivity
Authors: Chuntharpursat-Bon E , Povstyan OV , Ludlow MJ , Gaunt HJ , Baxter PD , Beech DJ
Published: April 2019

The discovery of Piezo1 channels as force sensors with roles in the endothelial response to fluid flow has appeared contradictory to earlier work suggesting mediation by a triad of cell adhesion molecules (CD31 and VE-cadherin) and vascular endothelial growth factor receptor 2 (VEGFR2). Here we propose an explanation. Stimulated emission depletion microscopy revealed physical proximity between Piezo1 and CD31 primarily at cell junctions. Förster resonance energy transfer measured by fluorescence lifetime imaging showed that the proteins approached to less than 10 nm. Substitution of a tyrosine residue at the distal C-terminus of CD31 prevented the interaction, suggesting intracellular association. The extracellular N-terminus also interacted, but exclusively at cell junctions. There was proximity between Piezo1 and VE-cadherin but not VEGFR2. Interaction with VE-cadherin was flow-dependent, consistent with additional recruitment after flow-sensing. CD31 suppressed mechanical sensitivity of Piezo1 channels and interacted with N-terminal Piezo1 propeller arms implicated in force sensing. The data suggest partnership between Piezo1 and adhesion molecules for sub cellular tuning of force response.
In-Silico Analysis of nsSNPs Associated with CYP11B2 Gene
Authors: Arooj Anam , Pervez Muhammad Tariq , Gillani Zeeshan , Chohan Tahir Ali , Tayyab Chaudhry M. , Babar Masroor Ellahi , Shah Asma Tufail
Published: April 2019

CYP11B2gene is located over the upper layer of the kidney. It produces aldosterone synthase enzyme and thereby has an essential role to balance salt and mineral level in the body. A mutation in this gene can deregulate the production of aldosterone hormone in the body which may lead to many diseases including hypertension and cardiac diseases. To control the excess production of this aldosterone an inhibitor “Fadrozole” is being used which is associated with an active site cavity of CYP11B2. This study has been divided into two parts. In the first part, the four computational tools (SIFT, Polyphen-2, I-Mutant, ConSurf) were used to identify 29 deleterious SNPs out of 1600CYP11B2SNPs. In the second part, five residues (R448G, R141P, W260R, F130S, and F445S) were identified in the active site cavity (out of 29 deleterious CYP11B2 SNPs) at the distance of 5A°. Binding free energy calculation as well as Dynamics simulation techniques were applied to determine the effect of these mutations on the CYP11B2-Fadrozole compound. The results showed thatFadrozolebinding with CYP11B2 became stronger which proved the efficiency of this drug inhibitor with these highly damaging mutations. Our study will be useful for selecting the high priority CYP11B2 mutations, which could be further, investigated in this gene-associated study, for better understanding of the structural and functional aspects of the observed (CYP11B2) protein.
The receptor-like kinases BAM1 and BAM2 promote the cell-to-cell movement of miRNA in the root stele to regulate xylem patterning
Authors: Fan Pengfei , Wang Hua , Xue Hao , Rosas-Diaz Tabata , Tang Weihua , Zhang Heng , Xu Lin , Lozano-Duran Rosa
Published: April 2019

Xylem patterning in the root is established through the creation of opposing gradients of miRNAs and their targets, enabled by the cell-to-cell spread of the former. The miRNAs involved in xylem patterning, miR165/6, move through plasmodesmata, but how their trafficking is regulated remains elusive. Here, we describe that the receptor-like kinases BAM1/2 are required for the intercellular movement of miR165/6 in the stele and hence proper xylem patterning in the root.
Risk of recurrent pregnancy loss in the Ukrainian population using a combined effect of genetic variants
Authors: Loizidou E. M , Kucherenko A. , Tatarskyy P. , Chernushyn S. , Livshyts G. , Gulkovskyi R. , Vorobiova I. , Antipkin Y. , Gorodna O. , Kaakinen M. A. , Prokopenko I. , Livshits L.
Published: April 2019

Recurrent pregnancy loss (RPL) affects nearly 5% of the women of reproductive age. Its heterogeneous and multifactorial nature complicate both diagnosis and treatment, as well as identification of the genetic contribution to RPL. Evidence about the aetiology of RPL is controversial; however, several biological mechanisms have been proposed. Given the current knowledge about the genetic susceptibility to idiopathic RPL, we aimed to evaluate the predictive ability of a combined variant panel to the risk of RPL in the Ukrainian sample of 114 cases and 106 healthy controls. We genotyped variants within the 12 genetic loci reflecting the main biological pathways involved in pregnancy maintenance: blood coagulation (F2, F5, F7, GP1A), hormonal regulation (ESR1, ADRB2), endometrium and placental function (ENOS, ACE), folate metabolism (MTHFR) and inflammatory response (IL6, IL8, IL10). We showed that a genetic risk score (GRS) calculated from the 12 variants was associated with an increased risk of RPL (odds ratio 1.56, 95% CI: 1.21,2.04,P=8.7×10−4). The receiver operator characteristic (ROC) analysis resulted in the area under the curve (AUC) of 0.64 (95% CI: 0.57, 0.72), indicating an improved ability of the GRS to classify women with and without RPL. In summary, implementation of the GRS approach can help defining women at higher risk to complex multifactorial conditions such as RPL. Future well-powered genome-wide association studies will help in the dissection of biological pathways not hypothesised previously for RPL and further improve the prediction and identification of those at risk for RPL.
Luteal progesterone level correlated with immunotherapy success of patients with repeated implantation failures
Authors: Sefrioui Omar , Madkour Aicha , Bouamoud Nouzha , Kaarouch Ismail , Saadani Brahim , Amzazi Saaïd , Copin Henri , Benkhalifa Moncef , Louanjli Noureddine ,   with the Lorem Ipsum Consortium
Published: April 2019

Immunotherapy using PBMC administration demonstrated relatively its effectiveness to treat RIF patients but it still unclear to explain some miscarriages. Luteal progesterone level (LPL) issued from corpus luteum after embryo implantation stage could be informative basis data to personalize immunotherapy for RIF patients predicting clinical outcomes. This randomized controlled study included 70 patients undergoing ICSI program presenting at least 3 RIF: 39 for Control of untreated patients and 31 for PBMC-test concerning treated patients with immunotherapy. For PBMC-test group, Peripheral Blood Mononuclear Cells (PBMCs) were isolated from patients on ovulation induction day and cultured three days to be administered to intrauterine cavity of patients two days before fresh embryo transfer. LPL was analyzed at day 15 after embryo transfer and clinical outcomes were calculated including implantation, clinical pregnancy and miscarriage rates. Clinical outcomes were doubly improved after immunotherapy including implantation and clinical pregnancy rates comparing Control versus PBMC-test (10% and 21% vs 24% and 45%). In the other hand, this strategy showed an increase over double in LPL (4ng/ml for Control vs 9ng/ml for PBMC-test) while the latter was correlated to clinical pregnancy. Bypassing the effectiveness of this immunotherapy approach for RIF patients, it is directly correlated to LPL proving the interactive reaction between immune profile of the treated patients and progesterone synthesis by corpus luteum.
Engineering a seven enzyme biotransformation using mathematical modelling and characterized enzyme parts
Authors: Finnigan William , Cutlan Rhys , Snajdrova Radka , Adams Joseph P. , Littlechild Jennifer A. , Harmer Nicholas J.
Published: April 2019

Multi-step enzyme reactions offer considerable cost and productivity benefits. Process models offer a route to understanding the complexity of these reactions, and allow for their optimization. Despite the increasing prevalence of multi-step biotransformations, there are few examples of process models for enzyme reactions. From a toolbox of characterized enzyme parts, we demonstrate the construction of a process model for a seven enzyme, three step biotransformation using isolated enzymes. Enzymes for cofactor regeneration were employed to make thisin vitroreaction economical. Good modelling practice was critical in evaluating the impact of approximations and experimental error. We show that the use and validation of process models was instrumental in realizing and removing process bottlenecks, identifying divergent behavior, and for the optimization of the entire reaction using a genetic algorithm. We validated the optimized reaction to demonstrate that complex multi-step reactions with cofactor recycling involving at least seven enzymes can be reliably modelled and optimized.

Significance statement

This study examines the challenge of modeling and optimizing multi-enzyme cascades. We detail the development, testing and optimization of a deterministic model of a three enzyme cascade with four cofactor regeneration enzymes. Significantly, the model could be easily used to predict the optimal concentrations of each enzyme in order to get maximum flux through the cascade. This prediction was strongly validated experimentally. The success of our model demonstrates that robust models of systems of at least seven enzymes are readily achievable. We highlight the importance of following good modeling practice to evaluate model quality and limitations. Examining deviations from expected behavior provided additional insight into the model and enzymes. This work provides a template for developing larger deterministic models of enzyme cascades.