bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the Efficacy of a Silver Carboxylate Antimicrobial Coating on Prosthetic Liners
Authors: Haglin Jack M. , Garcia Dioscaris R. , Roque Daniel L. , Spake Carole S.L. , Jarrell John D. , Born Christopher T. 
Published: August 2019

ABSTRACT

Introduction
One of the leading issues facing persons with amputation is late development of antibiotic-resistant bacterial infections of the residual limb. To reduce this infection risk, this study assessed the antimicrobial properties and profile of a silver carboxylate complex coating applied to samples of common prosthetic liner materials against pathogens frequently encountered in amputation-site infections.

Methods
The antimicrobial efficacy of the coating was measured utilizing a Kirby-Bauer assay with two different types of commercially available prosthetic liners. The assay was run against four pathogens including coagulase-negative Staphylococcus epidermidis, methicillin-sensitive Staphylococcus aureus, Enterococcus faecalis, and multidrug-resistant Acinetobacter baumannii. Observations of bacterial inhibition were made at 24-, 48-, and 72-hr time points for all four pathogens. Dose response curves were created to assess the relative efficacy of the coating against each pathogen independent of prosthetic liners. Graphite furnace atomic absorption spectroscopy (GFAAS) was utilized to measure coating silver elution at 24-, 48-, and 72-hr time points.

Results
All conditions of the coating were variably antimicrobial against all tested pathogens in the Kirby-Bauer analysis. Dose response analysis further demonstrated the coating's antimicrobial profile against all tested pathogens. GFAAS demonstrated consistent silver release of the coating throughout 72 hrs.

Conclusions
The results of this study suggest the tested antimicrobial coating is effective against a broad range of drug-resistant pathogens. Due to its ability to reduce and inhibit bacterial growth along the prosthetic liner surface, the coating shows promise as an effective tool toward mitigating infection and malodor found at the residual limb-liner interface among persons with amputation.
Patient-Centered Goal Setting in Developmental Therapy: Discordance between Documented Goals and Caregiver-Perceived Goals
Authors: Angeli Jennifer M. , Harpster Karen , Huijs Lobke , Seid Michael , Sheehan Amber , Schwab Sarah M. 
Published: August 2019

Introduction:
Productive interactions between engaged patients and clinical teams are key to effective clinical practice. Accordingly, the identification of needs and priorities through the process of collaborative goal setting is fundamental to patient-centered care. Executing a goal-setting process that is truly collaborative is challenging; many caregivers do not feel that they are adequately involved in the goal-setting process. This study presents the results of an initiative intended to understand goal concordance between therapists and caregivers.

Methods:
We conducted an observational, cross-sectional design study. Twenty-nine pediatric physical and occupational therapists developed and documented collaborative goals for their patients. Over 6 months, 120 randomly selected caregivers from a weekly list of patients scheduled for a follow-up physical or occupational therapy visit participated. Caregivers completed structured interviews related to their children’s therapy goals. We calculated agreement coefficients between caregiver-perceived goals and therapist-documented goals.

Results:
Overall strength of agreement was poor (M = −0.03, SD = 0.71). There were no significant differences within variables of a goal setter, goal importance, or goal utility. Median agreement coefficients were greatest for goals perceived to be identified solely by the caregiver, perceived as important, and perceived as functionally useful.

Conclusions:
The results of this study underscore the state of discordance in the collaborative goal-setting process in pediatric physical and occupational therapy. Healthcare encounters continue to be framed by provider perspectives and priorities. Developing therapy goals that enhance family involvement, relate to function, and are important to the healthcare consumer may improve the agreement.
Daily Changes in the Expression of Clock Genes in Sepsis and Their Relation with Sepsis Outcome and Urinary Excretion of 6-Sulfatoximelatonin
Authors: Acuña-Fernández Carlos , Marín Jorge Solera , Díaz-Casado María E. , Rusanova Iryna , Darias-Delbey Beneharo , Pérez-Guillama Luis , Florido-Ruiz Javier , Acuña-Castroviejo Darío 
Published: August 2019

ABSTRACT

Background:
Whereas the circadian system controls the daily production of melatonin and the daily activity of the immune system, increasing evidences support the association between circadian misalignment with the alterations in the immune response and melatonin rhythm during sepsis. The aim of this study was to analyze the daily changes in clock genes expression and the urinary excretion of 6-SM (6-sulfatoxymelatonin, the major melatonin metabolite), and their connection with the innate immune activity, oxidative status in blood, and clinical outcome during sepsis.

Methods:
Healthy volunteers, non-septic intensive care unit (ICU) patients, and septic ICU patients, were evaluated. The expression of bmal1, per2, clock, and cry1 genes was determined by polymerase chain reaction in blood; 6-SM was assessed in urine by ELISA; plasma cytokines IL-1β, IL-6, IL-8, TNFα, and IL-10 were determined by a multiplex array method, and lipid peroxidation (LPO) and protein oxidation (AOPP) by spectrophotometry. Hematological and biochemical data, and clinical scores of the patients, were also recorded.

Results:
Clock gene rhythm was maintained in non-septic patients but blunted in septic ones, whereas the innate immune and the oxidative stress responses were significantly higher in the latter. 6-SM excretion was also more elevated in septic than in non-septic patients, and it correlated with the degree of the immune response and oxidative status. 6-SM also correlated with SOFA and procalcitonin in the patients. Proinflammatory cytokines, LPO, and AOPP were normalized in the patients once recovered from sepsis.

Conclusion:
Our data suggest a relationship between clock genes rhythm disruption, the immune response, and the oxidative status, with 6-SM acting as a compensatory response. ICU conditions are not a main clock disrupter because of the significant differences found in the responses of septic versus non-septic patients under the same ICU environment.
Recovery of the gut microbiota after antibiotics depends on host diet and environmental reservoirs
Authors: Ng Katharine M. , Aranda-Diaz Andrés , Tropini Carolina , Frankel Matthew Ryan , Van Treuren William W. , O’Laughlin Colleen , Merrill Bryan D. , Yu Feiqiao Brian , Pruss Kali M. , Oliveira Rita Almeida , Higginbottom Steven K. , Neff Norma F. , Fischbach Michael A. , Xavier Karina B. , Sonnenburg Justin L. , Huang Kerwyn Casey 
Published: August 2019

SummaryThat antibiotics alter microbiota composition and increase infection susceptibility is well known, but their generalizable effects on the gut commensal community and dependence on environmental variables remain open questions. Here, we systematically compared antibiotic responses in gnotobiotic and conventional mice across antibiotics, microbiotas, diets, and housing status. We identify remarkable resilience, whereby a humanized microbiota recovers before drug administration ends, with transient dominance of resistant Bacteroides and taxa-asymmetric reduction in diversity. In other cases, in vitro sensitivities were not predictive of in vivo responses, underscoring the significance of host and community contexts. A fiber-deficient diet exacerbated collapse of the microbiota and delayed recovery, despite the presence of a similar core community across diets at the point of maximal disturbance. Resilience to a second ciprofloxacin treatment was observed via response reprogramming, in which species replacement after ciprofloxacin treatment established resilience to a second treatment, and also through cross housing transmission. Single-housing drastically disrupted recovery, highlighting the importance of environmental microbial reservoirs and suggesting sanitation may exacerbate the duration of antibiotic-mediated disruption. Our findings highlight the ability of the commensal microbiota to deterministically adapt to large perturbations, and the translational potential for modulating diet, sanitation, and microbiota composition during antibiotics.
Genome-wide association analysis of age-at-onset traits using Cox mixed-effects models
Authors: He Liang , Kulminski Alexander M. 
Published: August 2019

AbstractAge-at-onset is one of the critical phenotypes in cohort studies of age-related diseases. Large-scale genome-wide association studies (GWAS) of age-at-onset can provide more insights into genetic effects on disease progression, and transitions between different stages. Moreover, proportional hazards or Cox regression generally achieves higher statistical power in a cohort study than a binary trait using logistic regression. Although mixed-effects models are widely used in GWAS to correct for population stratification and family structure, application of Cox mixed-effects models (CMEMs) to large-scale GWAS are so far hindered by intractable computational intensity. In this work, we propose COXMEG, an efficient R package for conducting GWAS of age-at-onset using CMEMs. COXMEG introduces fast estimation algorithms for general sparse relatedness matrices including but not limited to block-diagonal pedigree-based matrices. COXMEG also introduces a fast and powerful score test for fully dense relatedness matrices, accounting for both population stratification and family structure. In addition, COXMEG handles positive semidefinite relatedness matrices, which are common in twin and family studies. Our simulation studies suggest that COXMEG, depending on the structure of the relatedness matrix, is 100∼100,000-fold computationally more efficient for GWAS than coxme for a sample consisting of 1000-10,000 individuals. We found that using sparse approximation of relatedness matrices yielded highly comparable performance in controlling false positives and statistical power for an ethnically homogeneous family-based sample. When applying COXMEG to a NIA-LOADFS sample with 3456 Caucasians, we identified theAPOE4variant with strong statistical power (p=1e-101), far more significant than previous studies using a transformed variable and a marginal Cox model. When investigating a multi-ethnic NIA-LOADFS sample including 3456 Caucasians and 287 African Americans, we identified a novel SNP rs36051450 (p=2e-9) nearGRAMD1B, the minor allele of which significantly reduced the hazards of AD in both genders. Our results demonstrated that COXMEG greatly facilitates the application of CMEMs in GWAS of age-at-onset phenotypes.
Top-down control of water intake by the endocannabinoid system
Authors: Zhao Zhe , Soria-Gómez Edgar , Varilh Marjorie , Julio-Kalajzić Francisca , Cannich Astrid , Castiglione Adriana , Vanhoutte Léonie , Duveau Alexia , Zizzari Philippe , Beyeler Anna , Cota Daniela , Bellocchio Luigi , Busquets-Garcia Arnau , Marsicano Giovanni 
Published: August 2019

AbstractWater intake is regulated by neocortical top-down circuits, but their identity and the cellular mechanisms involved are scantly known. Here, we show that endogenous activation of type-1 cannabinoid receptors (CB1) promotes water intake and that endocannabinoid modulation of excitatory projections from the anterior cingulate cortex to the basolateral amygdala is sufficient to guarantee physiological drinking. These data reveal a new circuit involved in the homeostatic control of water intake.
The gastrointestinal development ‘parts list’: transcript profiling of embryonic gut development in wildtype andRet-deficient mice
Authors: Chatterjee Sumantra , Nandakumar Priyanka , Auer Dallas R. , Gabriel Stacey B. , Chakravarti Aravinda 
Published: August 2019

AbstractThe development of the gut from endodermal tissue to an organ with multiple distinct structures and functions occurs over a prolonged time during embryonic days E10.5-E14.5 in the mouse. During this process, one major event is innervation of the gut by enteric neural crest cells (ENCC) to establish the enteric nervous system (ENS). To understand the molecular processes underpinning gut and ENS development, we generated RNA-seq profiles from wildtype mouse guts at E10.5, E12.5 and E14.5 from both sexes. We also generated these profiles from homozygousRetnull embryos, a model for Hirschsprung disease (HSCR), in whom the ENS is absent. These data reveal four major features: (1) between E10.5 to E14.5 the developmental genetic programs change from expression of major transcription factors (TF) and its modifiers to genes controlling tissue (epithelium, muscle, endothelium) specialization; (2) the major effect ofRetis not only on ENCC differentiation to enteric neurons but also on the enteric mesenchyme and epithelium; (3) a muscle genetic program exerts significant effects on ENS development, and (4) sex differences in gut development profiles are minor. The genetic programs identified, and their changes across development, suggests that both cell autonomous and non-autonomous factors, and interactions between the different developing gut tissues, are important for normal ENS development and its disorders.Significance statementThe mammalian gut is a complex set of tissues formed during development by orchestrating the timing of expression of many genes. Here we uncover the identity of these genes, their pathways and how they change during gut organogenesis. We used RNA-seq profiling in the wildtype mouse gut in both sexes during development (E10.5 - E14.5), as well as in aRetnull mouse, a model of Hirschsprung disease (HSCR). These studies have allowed us to expand the universe of genes and developmental processes that contribute to enteric neuronal innervation and to its dysregulation in disease.
Human bone marrow mesenchymal stem/stromal cell behaviour is coordinated via mechanically activated osteocyte-derived extracellular vesicles
Authors: Eichholz Kian F. , Woods Ian , Johnson Gillian P. , Shen Nian , Corrigan Michele , Labour Marie-Noelle , Wynne Kieran , Lowry Michelle C. , O’Driscoll Lorraine , Hoey David A. 
Published: August 2019

AbstractOsteocytes are mechanosensitive cells that are believed to play a fundamental role in coordinating bone mechanoadaptation via the secretion of paracrine factors. However, the exact mechanisms by which osteocytes relay mechanical signals to effector cells is poorly understood. In this study, we demonstrated that osteocytes subjected to a physiologic fluid shear secrete a distinct collection of factors that significantly enhance human MSC recruitment and osteogenesis. Utilising proteomics we generated an extensive map of proteins within the mechanically activated osteocyte secretome, identifying numerous paracrine factors that are modified by mechanical stimulation. Moreover, we identified the presence of extracellular vesicles (EVs) and further demonstrated that these mechanically activated osteocyte derived EVs (MAEVs) coordinate human MSCs recruitment and osteogenesis. This indicates that mechanical conditioning of parent cells can modify EVs and demonstrates the pro-osteogenic potential of MAEVs as a cell-free therapy to enhance bone regeneration and repair in diseases such as osteoporosis.
Expanding a Database-derived Biomedical Knowledge Graph via Multi-relation Extraction from Biomedical Abstracts
Authors: Nicholson David N. , Himmelstein Daniel S. , Greene Casey S. 
Published: August 2019

AbstractKnowledge graphs support multiple research efforts by providing contextual information for biomedical entities, constructing networks, and supporting the interpretation of high-throughput analyses. These databases are populated via some form of manual curation, which is difficult to scale in the context of an increasing publication rate. Data programming is a paradigm that circumvents this arduous manual process by combining databases with simple rules and heuristics written as label functions, which are programs designed to automatically annotate textual data. Unfortunately, writing a useful label function requires substantial error analysis and is a nontrivial task that takes multiple days per function. This makes populating a knowledge graph with multiple nodes and edge types practically infeasible. We sought to accelerate the label function creation process by evaluating the extent to which label functions could be re-used across multiple edge types. We used a subset of an existing knowledge graph centered on disease, compound, and gene entities to evaluate label function re-use. We determined the best label function combination by comparing a baseline database-only model with the same model but added edge-specific or edge-mismatch label functions. We confirmed that adding additional edge-specific rather than edge-mismatch label functions often improves text annotation and shows that this approach can incorporate novel edges into our source knowledge graph. We expect that continued development of this strategy has the potential to swiftly populate knowledge graphs with new discoveries, ensuring that these resources include cutting-edge results.
Non-oncology drugs are a source of previously unappreciated anti-cancer activity
Authors: Corsello Steven M. , Nagari Rohith T. , Spangler Ryan D. , Rossen Jordan , Kocak Mustafa , Bryan Jordan G. , Humeidi Ranad , Peck David , Wu Xiaoyun , Tang Andrew A. , Wang Vickie M. , Bender Samantha A. , Lemire Evan , Narayan Rajiv , Montgomery Philip , Ben-David Uri , Chen Yejia , Rees Matthew G. , Lyons Nicholas J. , McFarland James M. , Wong Bang T. , Wang Li , Dumont Nancy , O’Hearn Patrick J. , Stefan Eric , Doench John G. , Greulich Heidi , Meyerson Matthew , Vazquez Francisca , Subramanian Aravind , Roth Jennifer A. , Bittker Joshua A. , Boehm Jesse S. , Mader Christopher C. , Tsherniak Aviad , Golub Todd R. 
Published: August 2019

ABSTRACTAnti-cancer uses of non-oncology drugs have been found on occasion, but such discoveries have been serendipitous and rare. We sought to create a public resource containing the growth inhibitory activity of 4,518 drugs tested across 578 human cancer cell lines. To accomplish this, we used PRISM, which involves drug treatment of molecularly barcoded cell lines in pools. Relative barcode abundance following treatment thus reflects cell line viability. We found that an unexpectedly large number of non-oncology drugs selectively inhibited subsets of cancer cell lines. Moreover, the killing activity of the majority of these drugs was predictable based on the molecular features of the cell lines. Follow-up of several of these compounds revealed novel mechanisms. For example, compounds that kill by inducing PDE3A-SLFN12 complex formation; vanadium-containing compounds whose killing is dependent on the sulfate transporter SLC26A2; the alcohol dependence drug disulfiram, which kills cells with low expression of metallothioneins; and the anti-inflammatory drug tepoxalin, whose killing is dependent on high expression of the multi-drug resistance gene ABCB1. These results illustrate the potential of the PRISM drug repurposing resource as a starting point for new oncology therapeutic development. The resource is available at https://depmap.org.
A size principle for leg motor control inDrosophila
Authors: Azevedo Anthony W , Dickinson Evyn S , Gurung Pralaksha , Venkatasubramanian Lalanti , Mann Richard , Tuthill John C 
Published: August 2019

SummaryTo move the body, the brain must precisely coordinate patterns of activity among diverse populations of motor neurons. In many species, including vertebrates, the motor neurons innervating a given muscle fire in a specific order that is determined by a gradient of cellular size and electrical excitability. This hierarchy allows premotor circuits to recruit motor neurons of increasing force capacity in a task-dependent manner. However, it remains unclear whether such a size principle also applies to species with more compact motor systems, such as the fruit fly,Drosophila melanogaster, which has just 53 motor neurons per leg. Usingin vivocalcium imaging and electrophysiology, we found that genetically-identified motor neurons controlling flexion of the fly tibia exhibit a gradient of anatomical, physiological, and functional properties consistent with the size principle. Large, fast motor neurons control high force, ballistic movements while small, slow motor neurons control low force, postural movements. Intermediate neurons fall between these two extremes. In behaving flies, motor neurons are recruited in order from slow to fast. This hierarchical organization suggests that slow and fast motor neurons control distinct motor regimes. Indeed, we find that optogenetic manipulation of each motor neuron type has distinct effects on the behavior of walking flies.
Dormancy dynamics and dispersal contribute to soil microbiome resilience
Authors: Sorensen Jackson W , Shade Ashley 
Published: August 2019

AbstractIn disturbance ecology, stability is composed of resistance to change and resilience towards recovery after the disturbance subsides. Two key microbial mechanisms that can support microbiome stability include dormancy and dispersal. Specifically, microbial populations that are sensitive to disturbance can be re-seeded by local dormant pools of viable and reactivated cells, or by immigrants dispersed from regional metacommunities. However, it is difficult to quantify the contributions of these mechanisms to stability without, first, distinguishing the active from inactive membership, and, second, distinguishing the populations recovered by local resuscitation from those recovered by dispersed immigrants. Here, we investigate the contributions of dormancy dynamics (activation and inactivation), and dispersal to soil microbial community resistance and resilience. We designed a replicated, 45-week time-series experiment to quantify the responses of the active soil microbial community to a thermal press disturbance, including control mesocosms, disturbed mesocosms without dispersal, and disturbed mesocosms with dispersal after the release of the stressor. Communities were sensitive within one week of warming. Though the disturbed mesocosms did not fully recover within 29 weeks, resuscitation of thermotolerant taxa was key for community transition during the press, and both resuscitation of opportunistic taxa and immigration contributed to community resilience. Also, mesocosms with dispersal were more resilient than mesocosms without. This work advances the mechanistic understanding of how microbiomes respond to disturbances in their environment.