bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developing Leaders and Scholars in Health Care Improvement: The VA Quality Scholars Program Competencies
Authors: Horstman Molly J. , Miltner Rebecca S. , Wallhagen Margaret I. , Patrician Patricia A. , Oliver Brant J. , Roumie Christianne L. , Dolansky Mary A. , Perez Federico , Naik Aanand D. , Godwin Kyler M. 
Published: August 2020

Despite the need for leaders in health care improvement across health professions, there are no standards for the knowledge and skills that should be achieved through advanced interprofessional health care improvement training. Existing health care improvement training competencies focus on foundational knowledge expected of all trainees or for specific career pathways. Health care improvement leaders fill multiple roles within organizations and promote interprofessional improvement practice. The diverse skill set required of modern health care improvement leaders necessitates the development of training competencies specifically for fellowships in applied health care improvement.
The authors describe the development of the revised national Veterans Affairs Quality Scholars (VAQS) Program competencies. The VAQS Program is an interprofessional, postdoctoral training program whose mission is to develop leaders and scholars to improve health care. An interprofessional committee of VAQS faculty reviewed and revised the competencies over 4 months beginning in fall 2018. The first draft was developed using 111 competencies submitted by 11 VAQS training sites and a review of published competencies. The final version included 22 competencies spanning 5 domains: interprofessional collaboration and teamwork, improvement and implementation science, organization and system leadership, methodological skills and analytic techniques for improvement and research, and teaching and coaching.
Once attained, the VAQS competencies will guide the skill development that interprofessional health care improvement leaders need to participate in and lead health care improvement scholarship and implementation. These broad competencies are relevant to advanced training programs that develop health care improvement leaders and scholars and may be used by employers to understand the knowledge and skills expected of individuals who complete advanced fellowships in applied health care improvement.
Sound Practices: An Exploratory Study of Building and Monitoring Multiple-Choice Exams at Canadian Undergraduate Medical Education Programs
Authors: St-Onge Christina , Young Meredith , Renaud Jean-Sebastien , Cummings Beth-Ann , Drescher Olivia , Varpio Lara 
Published: August 2020

Purpose
Written examinations such as multiple-choice question (MCQ) exams are a key assessment strategy in health professions education (HPE), frequently used to provide feedback, to determine competency, or for licensure decisions. However, traditional psychometric approaches for monitoring the quality of written exams, defined as items that are discriminant and contribute to increase the overall reliability and validity of the exam scores, usually warrant larger samples than are typically available in HPE contexts. The authors conducted a descriptive exploratory study to document how undergraduate medical education (UME) programs ensure the quality of their written exams, particularly MCQs.

Method
Using a qualitative descriptive methodology, the authors conducted semistructured interviews with 16 key informants from 10 Canadian UME programs in 2018. Interviews were transcribed, anonymized, coded by the primary investigator, and co-coded by a second team member. Data collection and analysis were conducted iteratively. Research team members engaged in analysis across phases, and consensus was reached on the interpretation of findings via group discussion.

Results
Participants focused their answers around MCQ-related practices, reporting using several indicators of quality such as alignment between items and course objectives and psychometric properties (difficulty and discrimination). The authors clustered findings around 5 main themes: processes for creating MCQ exams, processes for building quality MCQ exams, processes for monitoring the quality of MCQ exams, motivation to build quality MCQ exams, and suggestions for improving processes.

Conclusions
Participants reported engaging multiple strategies to ensure the quality of MCQ exams. Assessment quality considerations were integrated throughout the development and validation phases, reflecting recent work regarding validity as a social imperative.
OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS OF MICROVASCULAR AND NEURAL CHANGES IN PRIMARY PULMONARY HYPERTENSION
Authors: Gu Simin , Li Zijing , Zhang Yichi , Liu Yingmei , Zeng Peng , Zeng Rui , Wang Wenhui , Xiao Jianhui 
Published: August 2020

Purpose:
To investigate the microvascular and neural changes in primary pulmonary hypertension (PPH) patients compared with healthy controls.

Methods:
Forty-four eyes of 22 PPH patients were included in this observational clinical cohort study, and 44 eyes of 22 healthy participants were enrolled as controls. Optical coherence tomography angiography images were obtained from each participant using the RTVue XR Avanti device with AngioVue software 2.0.

Results:
Regarding the total macular-associated vessel density, including that of the superficial and deep retina, the optic disk–associated capillary density, including that of the whole image, capillary density inside the disk, and the peripapillary region, was significantly lower in the PPH group than in the control group. There was a similar trend in the retinal nerve fiber layer thickness and the ganglion cell complex thickness, whereas the focal loss volume and the global loss volume were greater in the PPH group than the control group.

Conclusion:
Changes in the capillary density and thickness of the retina and the optic nerve head in PPH patients can be detected by optical coherence tomography angiography. Parameters including the macular-associated vessel density, optic disk–associated capillary density, retinal nerve fiber layer, ganglion cell complex, focal loss volume, and global loss volume may provide useful evidence for the early detection of microvascular and neural impairments in patients with PPH.
Cleft Palate Repair: A Study Between Two Surgical Procedures
Authors: Astrada Silvana , Bennun Ricardo D. 
Published: August 2020

Objective:
The purpose of this study was to categorize and compare outcomes and sequels in 2 groups of patients born with unilateral and bilateral complete cleft lip/palate, having their primary cleft palate repair performed in our hospital, by the same surgical team, during 2 different periods of time, to establish which of the 2 surgical reconstructive strategies employed was more effective to decrease sequels.

Material and Methods:
This is a randomized clinical trial including a total of 291, nonsyndromic patients, primary assisted in our Hospital, between 2002 and 2013, and operated by the same senior surgeon.
Two groups of patients of similar characteristics were treated utilizing 2 different surgical procedures according to the considered period. Isolated palates, syndromic patients, secondary and adult cases were considered as exclusion critters. Surgical data was obtained from medical records, and clinical examinations. All the patients were cautiously evaluated by a team expert to verify results, evolution, and sequels.

Results:
Statistically significant differences in the total percentage of complications were found between both groups. Group A: 54.85% and Group B: 21.90% (P value < 0.001).
Each complication was also considered by groups and estimated as follow:

Conclusions:
Based on the results of our research, we can suggest the Carstens’ variant plus the introduced modifications by the authors, as a useful surgical procedure to be utilized in primary complete unilateral or bilateral cleft palate repair to prevent post op common complications.
Malocclusion in Children Aged 8 to 10 Years Old With Operated Isolated Cleft Palate
Authors: Bené de Oliveira Maria Eduarda , Borba da Rocha Cordeiro Natália , de Andrade Veras Samuel Rodrigo , Costa de Melo Edna Maria , Viana do Vale Dione Maria , França Gurgel Ludmila Galindo , Santos da Figueira Manoela Almeida 
Published: August 2020

Abstract
This study aims to characterize dental malocclusion in children with operated isolated cleft palate aged 8 to 10 years old. Cross-sectional study with medical charts and complementary orthodontics exams and a sample for convenience. The study population was children aged 8 to 10 years registered at a Brazilian center from 2005 to 2009, diagnosed with isolated cleft palate and operated. the population of children registered at a Brazilian center from 2005 to 2009, diagnosed with isolated cleft palate. The data obtained from clinical records were analyzed by 2 orthodontists using the initial orthodontic documentation. The variables were: isolated cleft, sex, time of palatoplasty, malocclusion. The statistics included chi-square and Fisher exact tests (error 5%) to assess the malocclusion according to sex, type of cleft palate and time at palatoplasty. The sample resulted in 28 children (50% males, 50% females), average 8.5 years of age; the inter arch Class III relation was predominant (41.7%); a normal transverse relation was present in 48.1% of the sample; the majority presented a normal position of the upper incisors (61.5%);anterior open bite and excessive overjet was observed in 15.4% each and anterior cross-bite in 40.7%. There was no significant association between malocclusion with cleft type and surgery timing. The association between malocclusion and sex was significant (P = 0.049). Class III malocclusion was observed in most cases and females showed worse occlusal relations. Early orthodontic treatment is necessary in these patients.
Reconstruction of a Full-thickness Lateral Alar Defect Using a Superiorly Based Folded Nasolabial Flap Without a Cartilage Graft: A Single-stage Operation
Authors: Kim Hyeon Seok , Kim Woo Seob , Kim Han Koo , Bae Tae Hui 
Published: August 2020

Abstract
When reconstructing a lateral alar defect of the nose, satisfactory aesthetic and functional results are difficult to achieve through a single-stage surgery alone. Here the authors describe a new innovative surgical technique using a superiorly based folded nasolabial flap through a single-stage surgery alone. An 85-year-old male patient visited plastic surgery clinic with sudden enlargement of a mass 3 or 4 days before the visit. On the basis of the biopsy test results, a diagnosis of basal cell carcinoma on the right lateral alar was made. A full-thickness lateral alar resection was performed while maintaining the shape of the right alar rim (outer skin defect: 2.2 × 2 cm2 and inner mucosal defect: 1.4 × 1.3 cm2). Next, a single-stage reconstruction with a superiorly based folded turnover nasolabial flap was performed for the full-thickness lateral alar defect. Six months after the reconstructive surgery, no wound complication and nostril collapse occurred. The surgical method used in this case has many advantages. First, the authors’ method is performed only in a single stage. Second, the flap is based on a rich vascular supply from the angular artery, which eliminates the possibility of flap necrosis through multiple turnovers. Third, because the turnover nasolabial flap is a construct of the epidermis, dermis, and subcutaneous fat, the flap is quite stiff thus reducing the possibility of nostril collapse. Fourth, the procedure leaves no scars in the superior area of the nose other than the nasolabial fold scar.
Noninvasive prenatal exome sequencing inefficient for detecting single-gene disorders – problems and possible solutions
Authors: Filer Dayne L , Mieczkowski Piotr A , Brandt Alicia , Gilmore Kelly L , Powell Bradford C , Berg Jonathan S , Wilhelmsen Kirk C , Vora Neeta L 
Published: August 2020

AbstractWhat’s already known about this topic?Sequencing-based noninvasive testing can detect large copy number abnormalities and some auto-somal dominant single-gene disordersExome sequencing (ES) on fetal samples provides 20% diagnostic yield for structural abnormalities after normal karyotype & microarrayWhat does this study add?ES on cell-free DNA in three gravid patients with suspected genetic disease in the fetusWe demonstrate broad sequencing approaches are limited by sampling and technical difficulties, concluding broad sequencing is currently inappropriate for noninvasive testing
Capturing and Recreating Diverse Antibody Repertoires as Multivalent Recombinant Polyclonal Antibody Drugs
Authors: Keating Sheila M. , Mizrahi Rena A. , Adams Matthew S. , Asensio Michael A. , Benzie Emily , Carter Kyle P. , Chiang Yao , Edgar Robert C. , Gautam Bishal K. , Gras Ashley , Leong Jackson , Leong Renee , Lim Yoong Wearn , Manickam Vishal A. , Medina-Cucurella Angelica V. , Niedecken Ariel R. , Saini Jasmeen , Simons Jan Fredrik , Spindler Matthew J. , Stadtmiller Kacy , Tinsley Brendan , Wagner Ellen K. , Wayham Nicholas , Tracy LaRee , Lundberg Carina Vingsbo , Büscher Dirk , Terencio Jose Vicente , Roalfe Lucy , Pearce Emma , Richardson Hayley , Goldblatt David , Ramjag Anushka T. , Carrington Christine V.F. , Simmons Graham , Muench Marcus O. , Chamow Steven M. , Monroe Bryan , Olson Charles , Oguin Thomas H. , Lynch Heather , Jeanfreau Robert , Meyer Everett H. , Adler Adam S. , Johnson David S. 
Published: August 2020

ABSTRACTPlasma-derived polyclonal antibodies are polyvalent drugs used for many important clinical indications that require modulation of multiple drug targets simultaneously, including emerging infectious disease and transplantation. However, plasma-derived drugs suffer many problems, including low potency, impurities, constraints on supply, and batch-to-batch variation. In this study, we demonstrated proofs-of-concept for a technology that uses microfluidics and molecular genomics to capture diverse mammalian antibody repertoires as multivalent recombinant drugs. These “recombinant hyperimmune” drugs comprised thousands to tens of thousands of antibodies and were derived from convalescent human donors, or vaccinated human donors or immunized mice. Here we used our technology to build a highly potent recombinant hyperimmune for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) in less than three months. We also validated a recombinant hyperimmune for Zika virus disease that abrogates antibody-dependent enhancement (ADE) through Fc engineering. For patients with primary immune deficiency (PID), we built high potency polyvalent recombinant hyperimmunes against pathogens that commonly cause serious lung infections. Finally, to address the limitations of rabbit-derived anti-thymocyte globulin (ATG), we generated a recombinant human version and demonstrated in vivo function against graft-versus-host disease (GVHD). Recombinant hyperimmunes are a novel class of drugs that could be used to target a wide variety of other clinical applications, including cancer and autoimmunity.
Microbiota-Mediated Competition BetweenDrosophilaSpecies
Authors: Rombaut Antoine , Gallet Romain , Qitout Kenza , Samy Mukherjy , Guilhot Robin , Ghirardini Pauline , Lazzaro Brian P. , Becher Paul G. , Xuéreb Anne , Gibert Patricia , Fellous Simon 
Published: August 2020

AbstractSpecies that share resources often avoid competition with context-dependent behaviors. This is the case for the invasive insect pestDrosophila suzukii, whose larval ecological niche overlaps with that ofDrosophila melanogasterin ripe, but not rotten, fruit. We discoveredD. suzukiifemales prevent costly interspecific larval competition by avoiding oviposition on substrates previously visited byD. melanogaster. More precisely,D. melanogasterassociation with gut bacteria of the genusLactobacillustriggersD. suzukiiavoidance. However,D. suzukiiavoidance behavior is condition-dependent, andD. suzukiifemales that themselves carryD. melanogasterbacteria stop avoiding sites visited byD. melanogaster. The adaptive significance of avoiding cues from the competitor’s microbiota was revealed by experimentally reproducing in-fruit larval competition: reduced survival of D. suzukii larvae was dependent on the presence of gut bacteria in the competitor. This study unveils a new role for the symbiotic microbiota and plastic behaviors in mediating interspecific competition.
Non-canonical Hedgehog signaling regulates spinal cord and muscle regeneration
Authors: Hamilton Andrew M. , Borodinsky Laura N. 
Published: August 2020

AbstractInducing regeneration in injured spinal cord represents one of modern medicine’s greatest challenges. Research from a variety of model organisms indicates that Hedgehog (Hh) signaling may be a useful target to drive regeneration. However, the mechanisms of Hedgehog signaling-mediated tissue regeneration remain unclear. Here we examined Hh signaling during post-amputation tail regeneration inXenopus laevislarvae. We found that while Smoothened (Smo) activity is essential for proper spinal cord and skeletal muscle regeneration, transcriptional activity of the canonical Hh effector Gli is repressed immediately following amputation, and inhibition of Gli1/2 expression or transcriptional activity has minimal effects on regeneration. In contrast, we demonstrate that protein kinase A (PKA) is necessary for regeneration of both muscle and spinal cord, in concert with and independent of Smo respectively, and that its downstream effector CREB is activated in spinal cord following amputation. Our findings indicate that non-canonical mechanisms of Hh signaling are necessary for spinal cord and muscle regeneration.
Slow AMPA receptors in hippocampal principal cells
Authors: Pampaloni Niccolò Paolo , Riva Irene , Carbone Anna , Plested Andrew J. R. 
Published: August 2020

SummaryGlutamate receptor ion channels such as the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor mediate the majority of fast excitatory neurotransmission in the vertebrate CNS. AMPA receptors canonically provide the fast, millisecond component of the synaptic current. However, we found that about two-thirds of principal cells in the mouse hippocampus express AMPA receptors that do not desensitize and stay active for up to half a second. These receptors are expressed at synapses with a sparse but flat spatial distribution. The resulting increase in charge transfer allows single connections to reliably trigger action potentials. Biophysical and pharmacological observations imply that slow AMPA receptors incorporate γ-8 and other auxiliary proteins, and their activation lengthens individual miniature synaptic currents. Synaptic connections harboring slow AMPARs should have unique roles in hippocampal function.
An Optimal Control Approach for Enhancing Natural Killer Cells’ Secretion of Cytolytic Molecules
Authors: Makaryan Sahak Z. , Finley Stacey D. 
Published: August 2020

ABSTRACTNatural killer (NK) cells are immune effector cells that can detect and lyse cancer cells. However, NK cell exhaustion, a phenotype characterized by reduced secretion of cytolytic models upon serial stimulation, limits the NK cell’s ability to lyse cells. In this work, we investigatedin silicostrategies that counteract the NK cell’s reduced secretion of cytolytic molecules. To accomplish this goal, we constructed a mathematical model that describes the dynamics of the cytolytic molecules granzyme B (GZMB) and perforin-1 (PRF1) and calibrated the model predictions to published, experimental data using a Bayesian parameter estimation approach. We applied an information-theoretic approach to perform a global sensitivity analysis, from which we found the suppression of phosphatase activity maximizes the secretion of GZMB and PRF1. However, simply reducing the phosphatase activity is shown to deplete the cell’s intracellular pools of GZMB and PRF1. Thus, we added a synthetic Notch (synNotch) signaling circuit to our baseline model as a method for controlling the secretion of GZMB and PRF1 by inhibiting phosphatase activity and increasing production of GZMB and PRF1. We found the optimal synNotch system depends on the frequency of NK cell stimulation. For only a few rounds of stimulation, the model predicts inhibition of phosphatase activity leads to more secreted GZMB and PRF1; however, for many rounds of stimulation, the model reveals that increasing production of the cytolytic molecules is the optimal strategy. In total, we developed a mathematical framework that provides actionable insight into engineering robust NK cells for clinical applications.
Evaluation of Synergy Extrapolation for Predicting Unmeasured Muscle Excitations from Measured Muscle Synergies
Authors: Ao Di , Shourijeh Mohammad S. , Patten Carolynn , Fregly Benjamin J. 
Published: August 2020

AbstractElectromyography (EMG)-driven musculoskeletal modeling relies on high-quality measurements of muscle electrical activity to estimate muscle forces. However, a critical challenge for practical deployment of this approach is missing EMG data from muscles that contribute substantially to joint moments. This situation may arise due to either the inability to measure deep muscles with surface electrodes or the lack of a sufficient number of EMG electrodes. Muscle synergy analysis is a dimensionality-reduction approach to decompose a large number of muscle excitations into a small number of time-varying synergy excitations along with time-invariant synergy weights that define the contribution of each corresponding synergy excitation to a specific muscle excitation. This study evaluates how accurately missing muscle excitations can be predicted using synergy excitations extracted from muscles with available EMGs (henceforth called “synergy extrapolation”). The results were reported on a gait dataset collected from a stroke survivor walking on an instrumented treadmill at self-selected and fastest-comfortable speeds. The evaluation process started with full calibration of a lower-body EMG-driven model using 16-channel EMGs (including surface and indwelling) in each leg. One indwelling EMG (either iliopsoas or adductor longus) was then treated as unmeasured at a time. The synergy weights associated with the unmeasured muscle were predicted through solving a nonlinear optimization problem where the errors between inverse dynamics and EMG-driven joint moments were minimized. We also quantitatively evaluated how synergy analysis algorithms (principal component analysis (PCA) and non-negative matrix factorization (NMF)), EMG normalization methods, and number of synergies affect the accuracy of the predicted unmeasured muscle excitation. Synergy extrapolation performance was most influenced by the choice of synergy analysis algorithm and number of synergies. PCA with 5 or 6 synergies consistently predicted unmeasured muscle excitations most accurately and with greatest robustness to choice of EMG normalization method. Furthermore, the associated joint moment matching accuracy was comparable to that produced by the full EMG-driven calibration. The synergy extrapolation method described in this study may facilitate the assessment of human neuromuscular control and biomechanics in response to surgical or rehabilitation treatment when important EMG signals are missing.