bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic variants and cognitive functions in patients with brain tumors
Authors: Correa Denise D , Satagopan Jaya , Martin Axel , Braun Erica , Kryza-Lacombe Maria , Cheung Kenneth , Sharma Ajay , Dimitriadoy Sofia , O’Connell Kelli , Leong Siok , Karimi Sasan , Lyo John , DeAngelis Lisa M , Orlow Irene 
Published: May 2019

AbstractBackgroundPatients with brain tumors treated with radiotherapy (RT) and chemotherapy (CT) often experience cognitive dysfunction. We reported that single nucleotide polymorphisms (SNPs) in the APOE, COMT, and BDNF genes may influence cognition in brain tumor patients. In this study, we assessed whether genes associated with late-onset Alzheimer’s disease (LOAD), inflammation, cholesterol transport, dopamine and myelin regulation, and DNA repair may influence cognitive outcome in this population.MethodsOne hundred and fifty brain tumor patients treated with RT ± CT or CT alone completed a neurocognitive assessment and provided a blood sample for genotyping. We genotyped genes/SNPs in these pathways: (i) LOAD risk/inflammation/cholesterol transport, (ii) dopamine regulation, (iii) myelin regulation, (iv) DNA repair, (v) blood–brain barrier disruption, (vi) cell cycle regulation, and (vii) response to oxidative stress. White matter (WM) abnormalities were rated on brain MRIs.ResultsMultivariable linear regression analysis with Bayesian shrinkage estimation of SNP effects, adjusting for relevant demographic, disease, and treatment variables, indicated strong associations (posterior association summary [PAS] ≥ 0.95) among tests of attention, executive functions, and memory and 33 SNPs in genes involved in: LOAD/inflammation/cholesterol transport (eg, PDE7A, IL-6), dopamine regulation (eg, DRD1, COMT), myelin repair (eg, TCF4), DNA repair (eg, RAD51), cell cycle regulation (eg, SESN1), and response to oxidative stress (eg, GSTP1). The SNPs were not significantly associated with WM abnormalities.ConclusionThis novel study suggests that polymorphisms in genes involved in aging and inflammation, dopamine, myelin and cell cycle regulation, and DNA repair and response to oxidative stress may be associated with cognitive outcome in patients with brain tumors.
The Impact of Spinal Needle Selection on Postdural Puncture Headache: A Meta-Analysis and Metaregression of Randomized Studies
Authors: Zorrilla-Vaca A. , Mathur V. , Wu C.L. , Grant M.C. 
Published: May 2019

(Reg Anesth Pain Med. 2018;43:502–508)
As the use of neuraxial anesthesia is potentially broadening, an increased understanding and prevention of postdural puncture headache (PDPH) is needed. While numerous studies have examined either needle gauge or design, there has not been a comprehensive study analyzing individual technical and patient-related factors. This meta-analysis aimed to examine the association between spinal needle characteristics and PDPH.
Extreme Nailing: Is It Safe to Allow Immediate Weightbearing After Intramedullary Nail Fixation of Extra-articular Distal Tibial Fractures (OTA/AO 43-A)?
Authors: Beebe Michael J. , Morwood Michael , Serrano Rafael , Quade Jonathan H. , Auston Darryl A. , Watson David T. , Sanders Roy W. , Mir Hassan R. 
Published: May 2019

Objectives:
To determine whether immediate weightbearing after intramedullary (IM) fixation of extra-articular distal tibial fractures (OTA/AO 43-A) results in a change in alignment before healing.

Design:
Retrospective review.

Setting:
Level 1 trauma center.

Intervention:
IM nailing of distal tibial fractures.

Patients/Participants:
Fifty-three patients with 54 fractures, all of whom could bear weight as tolerated postoperatively. Eighteen fractures were OTA/AO 43-A1, 20 OTA/AO 43-A2, and 16 OTA/AO 43-A3; 20 fractures were open.

Main Outcome Measurements:
Change in fracture alignment or loss of position.

Results:
Average change from initial angulation at final follow-up was 0.52 ± 1.49 degrees of valgus and 0.48 ± 3.14 degrees of extension. Final alignment was excellent in 14, acceptable in 28, and poor in 12; 2 fractures went from acceptable initial alignment to poor final alignment; and 2 fractures went from excellent to acceptable alignment. Seven fractures had an improvement in alignment over time. Two fractures required free-flap coverage and 4 required staged grafting because of bone loss. Ten fractures had an unplanned return to the operating room (5 for infected nonunion requiring implant exchange, 3 for infection requiring debridement without implant revision, and 2 for aseptic nonunion). No patient had revision for implant failure.

Conclusions:
Immediate weightbearing after IM fixation of extra-articular distal tibial fractures (OTA/AO 43-A) led to minimal change in alignment and seems to be safe for most patients. Complications were consistent with those reported in previous non-weightbearing cohorts.

Level of Evidence:
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Jessner’s Solution with Trichloroacetic Acid Chemical Peel: Optimizing Outcomes and Safety
Authors: Dayan Erez , Rohrich Rod J. 
Published: May 2019

Summary:
Trichloroacetic acid (TCA) is a versatile agent, efficacious in treating a spectrum of facial rhytids and dyschrommias at varying concentrations. TCA is commonly used in a 30%–35% concentration to achieve a medium-depth peel into the upper reticular dermis. The addition of Jessner’s solution before the TCA peel application leads to partial removal of epidermis, allowing for deeper penetration of the TCA. This combination is beneficial, as lower concentrations of TCA can be used for the same depth of peel, minimizing complications such as scarring.
Immunogenicity and Safety of a Quadrivalent Meningococcal ACWY-tetanus Toxoid Conjugate Vaccine 6 Years After MenC Priming as Toddlers
Authors: Nolan Terry , Booy Robert , Marshall Helen S. , Richmond Peter , Nissen Michael , Ziegler John B. , Baine Yaela , Traskine Magali , Jastorff Archana , Van der Wielen Marie 
Published: May 2019

Background:
We assessed immunogenicity, antibody persistence and safety of the meningococcal serogroups A, C, W and Y-tetanus toxoid (TT) conjugate vaccine (MenACWY-TT) in children primed as toddlers with MenC vaccine.

Methods:
This open, multicenter extension study enrolled children 84–95 months of age who had received one dose of the combined Haemophilus influenzae type b (Hib)-MenC-TT conjugate vaccine (HibMenC group) or Hib-TT and monovalent MenC (MCC)-CRM197 vaccines (Hib+MCC group) at 12–18 months of age, in the primary study. All participants received one dose of MenACWY-TT. We assessed immunogenicity against MenA, MenC, MenW and MenY at 1 month and 2 years postvaccination by serum bactericidal assay using baby rabbit complement (rSBA). Safety and reactogenicity were evaluated.

Results:
Six years post-MenC vaccination, <20% of children retained rSBA-MenC titers ≥1:8. At 1 month post-MenACWY-TT vaccination, vaccine response rates against all serogroups were high for both groups with ≥97.1% of children having rSBA ≥1:8. Two years postvaccination, ≥63.6% of children retained rSBA-MenA ≥1:8, and ≥87.9% for other serogroups. Geometric mean titers for all serogroups declined at 2 years post-MenACWY-TT vaccination, but remained ≥13 times higher than prevaccination levels. For both groups, pain (≤58.5%), redness (≤51.4%) and fatigue (≤27.0%) were the most frequently reported adverse events. No serious adverse events were reported.

Conclusions:
One dose of MenACWY-TT boosts protection against MenC in primed children, is safe and extends protection against MenA, MenW and MenY. Immunogenicity and safety were comparable in infants vaccinated with conjugated vaccine (HibMenC-TT) or the separate vaccines (Hib-TT and MCC-CRM197).
Update on empty nose syndrome: disease mechanisms, diagnostic tools, and treatment strategies
Authors: Gill Amarbir S. , Said Mena , Tollefson Travis T. , Steele Toby O. 
Published: May 2019

Purpose of review
To discuss the proposed pathophysiology of empty nose syndrome (ENS), summarize and evaluate the role of validated diagnostic tools in the diagnosis of ENS, and review the medical and surgical treatment strategies for patients with ENS.

Recent findings
Historically, ENS has been associated with a reduction in nasal turbinate size; new data suggest that impaired trigeminal nerve function may also play a role in the pathophysiology of the disease. The newly validated empty nose syndrome 6 item questionnaires and Cotton test are steps forward to standardize the diagnosis of ENS. Finally, there has been a marked increase in surgical treatment strategies to reconstitute turbinate volume with various implant materials.

Summary
The diagnosis of ENS remains controversial but the last several years have seen a rejuvenation of interest in this disease entity. The validated empty nose syndrome 6 item questionnaires and Cotton test provide a standardized and objective means by which to characterize ENS. Prevention of iatrogenic ENS through avoidance of excessive turbinate reduction remains critical in preventing paradoxical nasal obstruction. Nasal humidification, patient education, and treatment of possible concomitant medical conditions (e.g., depression) constitute first lines of treatment. We support the cautious use of these screening tools as adjuncts to clinical decision-making. Although injectable implants to augment turbinate volume show promise as a therapeutic surgical technique, there is insufficient data to fully support their use at this time.
The Effect of Variations in Force Feedback in a Virtual Reality Environment on the Performance and Satisfaction of Dental Students
Authors: de Boer Ilse R. , Lagerweij Maxim D. , Wesselink Paul R. , Vervoorn Johanna M. 
Published: May 2019

Introduction
The aim of this study was to investigate the transfer of skills between various levels of force feedback (FFB) using the Simodont dental trainer (Moog, Nieuw-Vennep, the Netherlands). Students practiced a manual dexterity exercise in a virtual reality environment at a standard level of FFB and then were tested at the standard and an altered level of FFB. In addition, the students' satisfaction with the training exercise was evaluated.

Methods
One hundred twenty-six first-year dental students were randomly distributed into four groups and underwent a manual dexterity test in the virtual reality environment with automatic assessment after a 3-month period of practicing with standard FFB. The test consisted of drilling with the standard FFB and an altered level of FFB to evaluate the effect on performance. After the test, the participants completed a questionnaire.

Results
The results showed that 74% of the students who passed completed between one of three and three of three successful attempts at FFB levels at which they had not previously practiced.

Conclusions
The results of this study imply that if students practice a sufficient amount of time at one level of FFB, a skill is transferable from one level of FFB to another.
Virtual Standardized Patient Simulation
Authors: Bond William F. , Lynch Teresa J. , Mischler Matthew J. , Fish Jessica L. , McGarvey Jeremy S. , Taylor Jason T. , Kumar Dipen M. , Mou Kyle M. , Ebert-Allen Rebecca A. , Mahale Dilip N. , Talbot Thomas B. , Aiyer Meenakshy 
Published: May 2019

Introduction
High-value care (HVC) suggests that good history taking and physical examination should lead to risk stratification that drives the use or withholding of diagnostic testing. This study describes the development of a series of virtual standardized patient (VSP) cases and provides preliminary evidence that supports their ability to provide experiential learning in HVC.

Methods
This pilot study used VSPs, or natural language processing–based patient avatars, within the USC Standard Patient platform. Faculty consensus was used to develop the cases, including the optimal diagnostic testing strategies, treatment options, and scored content areas. First-year resident physician learners experienced two 90-minute didactic sessions before completing the cases in a computer laboratory, using typed text to interview the avatar for history taking, then completing physical examination, differential diagnosis, diagnostic testing, and treatment modules for each case. Learners chose a primary and 2 alternative “possible” diagnoses from a list of 6 to 7 choices, diagnostic testing options from an extensive list, and treatments from a brief list ranging from 6 to 9 choices. For the history-taking module, both faculty and the platform scored the learners, and faculty assessed the appropriateness of avatar responses. Four randomly selected learner-avatar interview transcripts for each case were double rated by faculty for interrater reliability calculations. Intraclass correlations were calculated for interrater reliability, and Spearman ρ was used to determine the correlation between the platform and faculty ranking of learners' history-taking scores.

Results
Eight VSP cases were experienced by 14 learners. Investigators reviewed 112 transcripts (4646 learner query-avatar responses). Interrater reliability means were 0.87 for learner query scoring and 0.83 for avatar response. Mean learner success for history taking was scored by the faculty at 57% and by the platform at 51% (ρ correlation of learner rankings = 0.80, P = 0.02). The mean avatar appropriate response rate was 85.6% for all cases. Learners chose the correct diagnosis within their 3 choices 82% of the time, ordered a median (interquartile range) of 2 (2) unnecessary tests and completed 56% of optimal treatments.

Conclusions
Our avatar appropriate response rate was similar to past work using similar platforms. The simulations give detailed insights into the thoroughness of learner history taking and testing choices and with further refinement should support learning in HVC.
Physician Versus Nonphysician Instruction
Authors: Musits Andrew N. , Phrampus Paul E. , Lutz John W. , Bear Todd M. , Maximous Stephanie I. , Mrkva Andrew J. , O'Donnell John M. 
Published: May 2019

IntroductionHealthcare simulation supports educational opportunities while maintaining patient safety. To reduce costs and increase the availability of training, a randomized controlled study evaluated central venous catheter (CVC) insertion training in the simulation laboratory with nonphysician competent facilitators (NPCFs) as instructors.MethodA group of learners naive to central line placement participated in a blended curriculum consisting of interactive online materials and simulation-based training. Learners were randomized to training with NPCFs or attending physician faculty. The primary outcome was simulated CVC insertion task performance, graded with a validated checklist by blinded physician reviewers. Learner knowledge and satisfaction were also evaluated. Analysis was conducted using noninferiority testing.ResultsEighty-five students, 11 attending physicians, and 7 NPCFs voluntarily participated. Noninferiority testing of the difference in CVC insertion performance between NPCF-trained learners versus physician-trained learners found no significant difference [rejecting the null hypothesis of inferiority using an 8% noninferiority margin (P< 0.01)]. In addition, there was no difference found between the 2 groups on pre/post knowledge scores, self-reported learner comfort, course satisfaction, or instructor satisfaction.ConclusionsAn introductory CVC curriculum can be taught to novice learners by carefully trained and supported NPCFs and achieve skill and knowledge outcomes similar to learners taught by physicians.
Simulating emotions: An active inference model of emotional state inference and emotion concept learning
Authors: Smith Ryan , Parr Thomas , Friston Karl J. 
Published: May 2019

AbstractThe ability to conceptualize and understand one’s own affective states and responses – or “emotional awareness” (EA) – is reduced in multiple psychiatric populations; it is also positively correlated with a range of adaptive cognitive and emotional traits. While a growing body of work has investigated the neurocognitive basis of EA, the neurocomputational processes underlying this ability have received limited attention. Here, we present a formal Active Inference (AI) model of emotion conceptualization that can simulate the neurocomputational (Bayesian) processes associated with learning about emotion concepts and inferring the emotions one is feeling in a given moment. We validate the model and inherent constructs by showing (i) it can successfully acquire a repertoire of emotion concepts in its “childhood”, as well as (ii) acquire new emotion concepts in synthetic “adulthood,” and (iii) that these learning processes depend on early experiences, environmental stability, and habitual patterns of selective attention. These results offer a proof of principle that cognitive-emotional processes can be modeled formally, and highlight the potential for both theoretical and empirical extensions of this line of research on emotion and emotional disorders.
Quantification of bioagressors induced yield gap for grain crops in France
Authors: Devaud Nathan G.F. , Barbu Corentin M. 
Published: May 2019

AbstractAnalyzing yield losses of crops is instrumental in sustaining high productivity. Here, we develop statistical modelling of yield losses by French department based on weather, soil and epidemiological data for 13 diseases and 12 insect pests of grain crops over 8 years. Those environmental factors explain up to 90% of yield variations (wheat). Weather and soil quality are first order determinants as manifested both by direct assessment and by strongly correlated yields of even taxonomically very different crops. Bioagressors are important second order determinants: losses of 5 qx/ha (~7%) on wheat and 2 qx/ha (~15%) on winter oilseed rape. Across models based on conceptually different achievable yields, only Septoria tritici and Sitobion avenae on wheat, and Ceutorhynchus picitarsis and Ceutorhynchus assimilis on winter oilseed rape are consistently and significantly detrimental to yield. Those bioagressors seem not fully controlled which is compatible with empirical observations in the non academical litterature.HighlightsGrain crop yields of similar growing seasons are highly correlatedEnvironmental determinants explain up to 90% of yield variationsBioagressors induced yield variations of 5 to 20%Specific pests and diseases with less than perfect control are identified
Plasticity of cell migration resulting from mechanochemical coupling
Authors: Cao Yuansheng , Ghabache Elisabeth , Rappel Wouter-Jan 
Published: May 2019

AbstractEukaryotic cells can migrate using different modes, ranging from amoeboid-like, during which actin filled protrusions come and go, to keratocyte-like, characterized by a stable morphology and persistent motion. How cells can switch between these modes is still not well understood but waves of signaling events on the cell cortex are thought to play an important role in these transitions. Here we present a simple two component biochemical reaction-diffusion model based on relaxation oscillators and couple this to a model for the mechanics of cell deformations. Different migration modes, including amoeboid-like and keratocyte-like, naturally emerge through phase transitions determined by interactions between biochemical traveling waves, cell mechanics and morphology. The model predictions are explicitly verified by systematically reducing the protrusive force of the actin network in experiments using wild-typeDictyostelium discoideumcells. Our results indicate the importance of coupling signaling events to cell mechanics and morphology and may be applicable in a wide variety of cell motility systems.
The Clathrin adaptor AP-1 and the Rab-stabilizing chaperone Stratum act in two parallel pathways to control the activation of the Notch pathway in Drosophila
Authors: Bellec Karen , Gicquel Isabelle , Borgne Roland Le 
Published: May 2019

AbstractDrosophila sensory organ precursors divide asymmetrically to generate pIIa/pIIb cells whose identity relies on the differential activation of Notch during cytokinesis. While Notch is present apically and basally relative to the midbody at the pIIa-pIIb interface, only the basal pool of Notch is reported to contribute to Notch activation in the pIIa cell. Such proper intra-lineage signalling therefore requires appropriate apico-basal targeting of Notch, its ligand Delta and its trafficking partner Sanpodo. We previously reported that AP-1 and Stratum regulate the intracellular trafficking of Notch and Sanpodo from the trans-Golgi network to basolateral membrane. Loss of AP-1 or of Stratum caused mild Notch phenotype. Here, we report that the concomitant loss of AP-1 and Stratum result in the stabilization of the apical pool of Notch, Delta and Spdo, the loss of the basal pool of Notch at the pIIa-pIIb interface, and is associated with activation of Notch in the two SOP daughters. We propose that AP-1 and Stratum control two parallel pathways towards plasma membrane and that Notch intra-lineage signalling could also occur at the apical pIIa-pIIb interface.
Mitochondrial dynamics quantitatively revealed by STED nanoscopy with an enhanced squaraine variant probe
Authors: Yang Xusan , Yang Zhigang , He Ying , Shan Chunyan , Yan Wei , Wu Zhaoyang , Chai Peiyuan , Teng Junlin , Qu Junle , Xi Peng 
Published: May 2019

AbstractMitochondria play a critical role in generating energy to support the entire lifecycle of biological cells, yet it is still unclear how their morphological structures evolve to regulate their functionality. Conventional fluorescence microscopy can only provide ∼300 nm resolution, which is insufficient to visualize mitochondrial cristae. Here, we developed an enhanced squaraine variant dye (MitoESq-635) to study the dynamic structures of mitochondrial cristae in live cells at superresolution. The low saturation intensity and high photostability make it ideal for long-term, high-resolution STED nanoscopy. We demonstrate the time-lapsed imaging of the mitochondrial inner membrane over 50 minutes in living HeLa cells at 35.2 nm resolution for the first time. The forms of the cristae during mitochondrial fusion and fission can be clearly resolved. Our study demonstrates the emerging capability of optical STED nanoscopy to investigate intracellular physiological processes at nanoscale resolution for long periods of time with minimal phototoxicity.
GLUT4 expression and glucose transport in human induced pluripotent stem cell-derived cardiomyocytes
Authors: Bowman Peter R.T , Smith Godfrey L. , Gould Gwyn W. 
Published: May 2019

AbstractInduced pluripotent stem cell derived cardiomyocytes (iPSC-CM) have the potential to transform regenerative cardiac medicine and the modelling of cardiac disease. This is of particular importance in the context of diabetic cardiomyopathy where diabetic individuals exhibit reduced cardiac diastolic contractile performance in the absence of vascular disease, significantly contributing towards high cardiovascular morbidity. In this study, the capacity of iPSC-CM to act as a novel cellular model of cardiomyocytes was assessed. The diabetic phenotype is characterised by insulin resistance, therefore there was a specific focus upon metabolic parameters. Despite expressing crucial insulin signalling intermediates and relevant trafficking proteins, it was identified that iPSC-CM do not exhibit insulin-stimulated glucose uptake. iPSC-CM are spontaneously contractile however contraction mediated uptake was not found to mask any insulin response. The fundamental limitation identified in these cells was a critical lack of expression of the insulin sensitive glucose transporter GLUT4. Using comparative immunoblot analysis and the GLUT-selective inhibitor BAY-876 to quantify expression of these transporters, we show that iPSC-CM express high levels of GLUT1 and low levels of GLUT4 compared to primary cardiomyocytes and cultured adipocytes. Interventions to overcome this limitation were unsuccessful. We suggest that the utility of iPSC-CMs to study cardiac metabolic disorders may be limited by their apparent foetal-like phenotype.