bluuebunny/crossref_metadata_2025 huggingface dataset:
A faith-based mind–body intervention to improve psychosocial well-being among rural adults
Authors: Mama Scherezade K , Bhuiyan Nishat , Bopp Melissa J , McNeill Lorna H , Lengerich Eugene J , Smyth Joshua M
Published: August 2020

Churches are well positioned to promote better mental health outcomes in underserved populations, including rural adults. Mind–body (MB) practices improve psychological well-being yet are not widely adopted among faith-based groups due to conflicting religious or practice beliefs. Thus, “Harmony & Health” (HH) was developed as a culturally adapted MB intervention to improve psychosocial health in urban churchgoers and was adapted and implemented in a rural church. The purpose of this study was to explore the feasibility, acceptability, and efficacy of HH to reduce psychosocial distress in rural churchgoers. HH capitalized on an existing church partnership to recruit overweight or obese (body mass index [BMI] ≥25.0 kg/m2) and insufficiently active adults (≥18 years old). Eligible adults participated in an 8 week MB intervention and completed self-reported measures of perceived stress, depressive symptoms, anxiety, and positive and negative affect at baseline and postintervention. Participants (mean [M] age = 49.1 ± 14.0 years) were mostly women (84.8%), non-Hispanic white (47.8%) or African American (45.7%), high socioeconomic status (65.2% completed ≥bachelor degree and 37.2% reported an annual household income ≥$80,000), and obese (M BMI = 32.6 ± 5.8 kg/m2). Participants reported lower perceived stress (t = −2.399, p = .022), fewer depressive symptoms (t = −3.547, p = .001), and lower negative affect (t = −2.440, p = .020) at postintervention. Findings suggest that HH was feasible, acceptable, and effective at reducing psychosocial distress in rural churchgoers in the short-term. HH reflects an innovative approach to intertwining spirituality and MB practices to improve physical and psychological health in rural adults, and findings lend to our understanding of community-based approaches to improve mental health outcomes in underserved populations.
A scoping review of patient-facing, behavioral health interventions with voice assistant technology targeting self-management and healthy lifestyle behaviors
Authors: Sezgin Emre , Militello Lisa K , Huang Yungui , Lin Simon
Published: August 2020

Engaging in positive healthy lifestyle behaviors continues to be a public health challenge, requiring innovative solutions. As the market for voice assistants (Amazon Alexa, Google Assistant, and Apple Siri) grows and people increasingly use them to assist their daily tasks, there is a pressing need to explore how voice assistant (VA) technology may be used in behavioral health interventions. A scoping review of literature was conducted to address a PICO (Population, Intervention, Comparison, and Outcome) question: across populations, how does the use of voice assistants in behavioral health research/interventions influence healthy lifestyle behaviors versus control or comparison interventions? To inform the science, a secondary aim of this review was to explore characteristics of VAs used in behavioral health research. The review was conducted following Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines with scoping review extension (PRISMA-ScR). Ten studies satisfied the inclusion criteria, representing research published through February 2019. Studies spanned pediatric to elderly populations, covering a vast array of self-management and healthy lifestyle behaviors. The majority of interventions were multicomponent, involving more than one of the following behavior change techniques grouped by cluster: shaping knowledge, self-belief, repetition and substitution, feedback and monitoring, goals and planning, antecedents, natural consequences, comparison of behavior, and identification. However, most studies were in early stages of development, with limited efficacy trials. VA technology continues to evolve and support behavioral interventions using various platforms (e.g., Interactive Voice Response [IVR] systems, smartphones, and smart speakers) which are used alone or in conjunction with other platforms. Feasibility, usability, preliminary efficacy, along with high user satisfaction of research adapted VAs, in contrast to standalone commercially available VAs, suggest a role for VAs in behavioral health intervention research.
Positive psychology in health care: defining key stakeholders and their roles
Authors: Lianov Liana S , Barron Grace Caroline , Fredrickson Barbara L , Hashmi Sean , Klemes Andrea , Krishnaswami Janani , Lee Jenny , Le Pertel Noémie , Matthews Jessica A , Millstein Rachel A , Phillips Edward M , Sannidhi Deepa , Purpur de Vries Patty , Wallace Anne , Winter Sandra J
Published: August 2020

Lifestyle-related diseases have common risk factors: physical inactivity, poor diet, inadequate sleep, high stress, substance use, and social isolation. Evidence is mounting for the benefits of incorporating effective methods that promote healthy lifestyle habits into routine health care treatments. Research has established that healthy habits foster psychological and physiological health and that emotional well-being is central to achieving total well-being. The Happiness Science and Positive Health Committee of the American College of Lifestyle Medicine aims to raise awareness about strategies for prioritizing emotional well-being. The Committee advocates for collaborative translational research to adapt the positive psychology and behavioral medicine evidence base into methodologies that address emotional well-being in nonmental health care settings. Another aim is to promote health system changes that integrate evidence-based positive-psychology interventions into health maintenance and treatment plans. Also, the Committee seeks to ameliorate health provider burnout through the application of positive psychology methods for providers' personal health. The American College of Lifestyle Medicine and Dell Medical School held an inaugural Summit on Happiness Science in Health Care in May 2018. The Summit participants recommended research, policy, and practice innovations to promote total well-being via lifestyle changes that bolster emotional well-being. These recommendations urge stakeholder collaboration to facilitate translational research for health care settings and to standardize terms, measures, and clinical approaches for implementing positive psychology interventions. Sample aims of joint collaboration include developing evidence-based, practical, low-cost behavioral and emotional assessment and monitoring tools; grants to encourage dissemination of pilot initiatives; medical record dashboards with emotional well-being and related aspects of mental health as vital signs; clinical best practices for health care teams; and automated behavioral programs to extend clinician time. However, a few simple steps for prioritizing emotional well-being can be implemented by stakeholders in the near-term.
On Artificial Intelligence and Deep Learning Within Medical Education
Authors: Carin Lawrence
Published: August 2020

The methodology of deep learning, a component of machine learning and artificial intelligence, is introduced. The opportunity for this technology to automate some aspects of medical practice is reviewed. Finally, a discussion is provided on the integration of concepts from deep learning into medical education.
The Relationship Between Accreditation Cycle and Licensing Examination Scores: A National Look
Authors: Roy Marguerite , Wood Timothy J. , Blouin Danielle , Eva Kevin W.
Published: August 2020

Purpose

Accreditation aims to ensure all training programs meet agreed-upon standards of quality. The process is complex, resource intensive, and costly. Its benefits are difficult to assess because contextual confounds obscure comparisons between systems that do and do not include accreditation. This study explores accreditation’s influence “within system” by investigating the relationship between accreditation cycle and performance on a national licensing examination.

Method

Scores on the computer-based portion of the Medical Council of Canada Qualifying Examination Part I, from 1993 to 2017, were examined for all 17 Canadian medical schools. Typically completed upon graduation from medical school, results within each year were transformed for comparability across administrations and linked to timing within each school’s accreditation cycle. ANOVAs were used to assess the relationship between accreditation timing and examination scores. Secondary analyses isolated 4-year from 3-year training programs and separated data generated before versus after implementation of a national midcycle informal review program.

Results

Performance on the licensing exam was highest during and shortly after an accreditation site visit, falling significantly until the midpoint in the accreditation cycle (d = 0.47) before rising again. This pattern disappeared after introduction of informal interim review, but too little data have accumulated post implementation to determine if interim review is sufficient to break the influence of accreditation cycle.

Conclusions

Formal, externally driven, accreditation cycles appear associated with educational processes in ways that translated into student outcomes on a national licensing examination. Whether informal, internal, interim reviews can mediate this effect remains to be seen.
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

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

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

What’s already known about this topic?

Sequencing-based noninvasive testing can detect large copy number abnormalities and some auto-somal dominant single-gene disorders

Exome sequencing (ES) on fetal samples provides 20% diagnostic yield for structural abnormalities after normal karyotype & microarray

What does this study add?

ES on cell-free DNA in three gravid patients with suspected genetic disease in the fetus

We 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

Plasma-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

Species 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

Inducing 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

Glutamate 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

Natural 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

Electromyography (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.
Bayesian estimation of cell-type-specific gene expression per bulk sample with prior derived from single-cell data
Authors: Wang Jiebiao , Roeder Kathryn , Devlin Bernie
Published: August 2020

When assessed over a large number of samples, bulk RNA sequencing provides reliable data for gene expression at the tissue level. Single-cell RNA sequencing (scRNA-seq) deepens those analyses by evaluating gene expression at the cellular level. Both data types lend insights into disease etiology. With current technologies, however, scRNA-seq data are known to be noisy. Moreover, constrained by costs, scRNA-seq data are typically generated from a relatively small number of subjects, which limits their utility for some analyses, such as identification of gene expression quantitative trait loci (eQTLs). To address these issues while maintaining the unique advantages of each data type, we develop a Bayesian method (bMIND) to integrate bulk and scRNA-seq data. With a prior derived from scRNA-seq data, we propose to estimate sample-level cell-type-specific (CTS) expression from bulk expression data. The CTS expression enables large-scale sample-level downstream analyses, such as detecting CTS differentially expressed genes (DEGs) and eQTLs. Through simulations, we demonstrate that bMIND improves the accuracy of sample-level CTS expression estimates and power to discover CTS-DEGs when compared to existing methods. To further our understanding of two complex phenotypes, autism spectrum disorder and Alzheimer’s disease, we apply bMIND to gene expression data of relevant brain tissue to identify CTS-DEGs. Our results complement findings for CTS-DEGs obtained from snRNA-seq studies, replicating certain DEGs in specific cell types while nominating other novel genes in those cell types. Finally, we calculate CTS-eQTLs for eleven brain regions by analyzing GTEx V8 data, creating a new resource for biological insights.
Heterogenous susceptibility to R-pyocins in populations ofPseudomonas aeruginosasourced from cystic fibrosis lungs
Authors: Mei Madeline , Thomas Jacob , Diggle Stephen P.
Published: August 2020

Bacteriocins are proteinaceous antimicrobials produced by bacteria which are active against other strains of the same species. R-type pyocins are phage tail-like bacteriocins produced byPseudomonas aeruginosa. Due to their anti-pseudomonal activity, R-pyocins have potential as therapeutics in infection.P. aeruginosais a Gram-negative opportunistic pathogen and is particularly problematic for individuals with cystic fibrosis (CF).P. aeruginosafrom CF lung infections develop increasing resistance to antibiotics, making new treatment approaches essential.P. aeruginosapopulations become phenotypically and genotypically diverse during infection, however, little is known of the efficacy of R-pyocins against heterogeneous populations. R-pyocins vary by subtype (R1-R5), distinguished by binding to different residues on the lipopolysaccharide (LPS). Each type varies in killing spectrum, and each strain produces only one R-type. To evaluate the prevalence of different R-types, we screenedP. aeruginosastrains from the International Pseudomonas Consortium Database (IPCD) and from our biobank of CF strains. We found that (i) R1-types were the most prevalent R-type among strains from respiratory sources; (ii) there is a large number of strains lacking R-pyocin genes, and (iii) isolates collected from the same patient have the same R-type. We then assessed the impact of intra-strain diversity on R-pyocin susceptibility and found a heterogenous response to R-pyocins within populations, likely due to differences in the LPS core. Our work reveals that heterogeneous populations of microbes exhibit variable susceptibility to R-pyocins and highlights that there is likely heterogeneity in response to other types of LPS-binding antimicrobials, including phage.

Importance

R-pyocins have potential as alternative therapeutics againstPseudomonas aeruginosain chronic infection, however little is known about the efficacy of R-pyocins in heterogeneous bacterial populations.P. aeruginosais known to become resistant to multiple antibiotics, as well as evolve phenotypic and genotypic diversity over time; thus it is particularly difficult to eradicate in chronic cystic fibrosis (CF) lung infections. In this study, we found thatP. aeruginosapopulations from CF lungs maintain the same R-pyocin genotype but exhibit heterogeneity in susceptibility to R-pyocins from other strains. Our findings suggest there is likely heterogeneity in response to other types of LPS-binding antimicrobials, such as phage, highlighting the necessity of further studying the potential of LPS-binding antimicrobial particles as alternative therapies in chronic infections.
Persistent bacterial coinfection of a COVID-19 patient caused by a genetically adaptedPseudomonas aeruginosachronic colonizer
Authors: Qu Jiuxin , Cai Zhao , Liu Yumei , Duan XiangKe , Han Shuhong , Zhu Yuao , Jiang Zhaofang , Zhang Yingdan , Zhuo Chao , Liu Yang , Liu Yingxia , Liu Lei , Yang Liang
Published: August 2020

This study characterized a genetically adaptedPseudomonas aeruginosasmall colony variant isolated from a COVID-19 patient who suffered persistent bacterial coinfection and eventually recovered from critical illness. Specification and modification of the isolates discovered at genomic and transcriptomic levels with aligned phenotypic observations indicated that these isolates formed excessive biofilm with elevated quorum sensing systems.
Interpretation of exercise-induced changes in human skeletal muscle mRNA expression depends on the timing of the post-exercise biopsies
Authors: Kuang Jujiao , McGinley Cian , Lee Matthew J-C , Saner Nicholas J , Garnham Andrew , Bishop David J
Published: August 2020

Aim

Exercise elicits a range of adaptive responses in skeletal muscle that include changes in mRNA expression. To better understand the health benefits of exercise training, it is essential to investigate the underlying molecular mechanisms of skeletal muscle adaptations to exercise. However, most studies have assessed the molecular events at a few convenient time points within a short time frame post exercise, and the variations of gene expression kinetics have not been addressed systematically.

Method

Muscle biopsies were collected from nine participants at baseline and six time points (0, 3, 9, 24, 48, and 72 h) following a session of high-intensity interval exercise. We assessed the mRNA content of 23 gene isoforms from the muscle samples.

Result

The temporal patterns of target gene expression were highly variable and the mRNA contents detected were largely dependent on the muscle sample timing. The maximal levels of mRNA content of all tested target genes were observed between 3 to 48 h post exercise.

Conclusion

Our findings highlight a critical gap in knowledge regarding the molecular response to exercise, where the use of a few time points within a short period after exercise has led to an incomplete understanding of the molecular responses to exercise. The timing of muscle sampling for individual studies needs to be carefully chosen based on existing literature and preliminary analysis of the molecular targets of interest. We propose that a comprehensive time-course analysis on the exercise-induced transcriptional response in humans will significantly benefit the field of exercise molecular biology.
Rapid evolution promotes fluctuation-dependent species coexistence
Authors: Yamamichi Masato , Letten Andrew D.
Published: August 2020

Abstract

Recent studies have demonstrated that rapid contemporary evolution can play a significant role in regulating population dynamics on ecological timescales. Here we identify a previously unrecognized mode by which rapid evolution can promote species coexistence via temporal fluctuations and a trade-off between competitive ability and the speed of adaptive evolution. We show that this interaction between rapid evolution and temporal fluctuations not only increases the range of coexistence conditions under a gleaner-opportunist trade-off (i.e., low minimum resource requirement [R*] vs. high maximum growth rate), but also yields stable coexistence in the absence of a classical gleaner-opportunist trade-off. Given the propensity for both oscillatory dynamics and divergent rates of adaptation (including rapid evolution and phenotypic plasticity) in the real world, we argue that this expansion of fluctuation-dependent coexistence theory provides an important overlooked solution to the so-called ‘paradox of the plankton’.
The Epidemiology Characteristics of Positive COVID-19 patients in a Caribbean Territory
Authors: Gopaul Chavin D. , Ventour Dale , Trotman Michelle , Thomas Davlin
Published: August 2020

Background

The purpose of the study is to determine the epidemiology of COVID-19 in a Caribbean Territory by the characterisation of patients in terms of, the numbers, socio demographics and associated co-morbidities. This comparison was done between local cases and imported cases. There have been no prior studies on COVID-19 in the Caribbean and as such this paper attempts to discuss the patterns associated with COVID-19 patients in the Caribbean.

Methods

This study determined the epidemiology of COVID-19 in a Caribbean territory using retrospective data. Analysis was performed using Excel and SPSS 22.0.

Results

The majority of patients were female (61.9%) vs male (38.0%). The majority of the population were between 45 -64 yrs (43.4%) followed by above 65 at 28.8%. Cough was the most common presenting complaint at 44.9%, with fever being second 37.1%. The majority of female participants had a travel history at 61.9%, while males were 38.0 %. The occurrence of cough was high among both local cases (46.4%) and imported cases (47.6%).

Conclusions

These patterns can inform clinicians and other health care workers on the unique findings associated with COVID-19 positive patients especially those in the Caribbean region
Kinetics of viral clearance and antibody production across age groups in SARS-CoV-2 infected children
Authors: Bahar Burak , Jacquot Cyril , Mo Yunchuan D. , DeBiasi Roberta L. , Campos Joseph , Delaney Meghan
Published: August 2020

Objectives

To improve understanding of transition from viral infection to viral clearance, and antibody response in pediatric patients with SARS-CoV-2 infection.

Study design

This retrospective analysis of children tested for SARS-CoV-2 by RT-PCR and IgG antibody at a quaternary-care, free-standing pediatric hospital between March 13th, 2020 to June 21st, 2020 included 6369 patients who underwent PCR testing and 215 patients who underwent antibody testing. During the initial study period, testing focused primarily on symptomatic children; the later study period included asymptomatic patients who underwent testing as preadmission or preprocedural screening. We report the proportion of positive and negative tests, time to viral clearance, and time to seropositivity.

Results

The rate of positivity varied over time due to viral circulation in the community and transition from targeted testing of symptomatic patients to more universal screening of hospitalized patients. Median duration of viral shedding (RT-PCR positivity) was 19.5 days and RT-PCR negativity from positivity was 25 days. Of note, patients aged 6 to 15 years demonstrated a longer period of RT-PCR negativity from positivity, compared to patients aged 16 to 22 years (median=32 versus 18 days, p=0.015). Median time to seropositivity from RT-PCR positivity was 18 days while median time to reach adequate levels of neutralizing antibodies (defined as equivalent to 160 titer) was 36 days.

Conclusions

The majority of patients demonstrated a prolonged period of viral shedding after infection with SARS CoV-2. Whether this correlates with persistent infectivity is unknown. Only 17 of 33 patients demonstrated neutralizing antibodies, suggesting that some patients may not mount significant immune responses to infection. It remains unknown if IgG antibody production correlates with immunity and how long measurable antibodies persist and protect against future infection.
Performance assessment of 11 commercial serological tests for SARS-CoV-2 on hospitalized COVID-19 patients
Authors: Serre-Miranda C , Nobrega C , Roque S , Canto-Gomes J , Silva CS , Vieira N , Barreira-Silva P , Alves-Peixoto P , Cotter J , Reis A , Formigo M , Sarmento H , Pires O , Carvalho A , Petrovykh DY , Diéguez L , Sousa JC , Sousa N , Capela C , Palha JA , Cunha PG , Correia-Neves M
Published: August 2020

Commercial availability of serological tests to evaluate immunoglobulins (Ig) towards severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has grown exponentially since the onset of COVID-19 (Coronavirus Disease 2019) outbreak. Their thorough validation is of extreme importance before using them as epidemiological tools to infer population seroprevalence, and as complementary diagnostic tools to molecular approaches(e.g. RT-qPCR). Here we assayed commercial serological tests (semiquantitative and qualitative) from 11 suppliers in 126 samples collected from hospitalized COVID-19 patients, and from 36 healthy and HIV-infected individuals (collected at the pre-COVID-19 pandemic). Specificity was above 95% in 9 tests. Samples from COVID-19 patients were stratified by days since symptoms onset (<10, 10-15, 16-21 and >21 days). Tests sensitivity increases with time since symptoms onset, and peaks at 16-21 days for IgM and IgA (maximum: 91.2%); and from 16-21 to >21 days for IgG, depending on the test (maximum: 94.1%). Data from semiquantitative tests show that patients with severe clinical presentation have lower relative levels of IgM, IgA and IgG at <10 days since symptoms onset in comparison to patients with non-severe presentation. At >21 days since symptoms onset the relative levels of IgM and IgG (in one test) are significantly higher in patients with severe clinical presentation, suggesting a delay in the upsurge of Ig against SARS-CoV-2 in those patients.

This study highlights the high specificity of most of the evaluated tests, and sensitivity heterogeneity. Considering the virus genetic evolution and population immune response to it, continuous monitoring of commercially available serological tests towards SARS-CoV-2 is necessary.