bluuebunny/crossref_metadata_2025_split huggingface dataset:
In VitroEffects of Emerging Bisphenols on Myocyte Differentiation and Insulin Responsiveness
Authors: Jing Jiongjie , Pu Yong , Veiga-Lopez Almudena , Lyu Lihua 
Published: July 2020

AbstractBisphenols are endocrine disrupting chemicals to which humans are ubiquitously exposed to. Prenatal bisphenol A exposure can lead to insulin resistance. However, the metabolic effects of other emerging bisphenols, such as bisphenol S (BPS) and bisphenol F (BPF), are less understood. Because the skeletal muscle is the largest of the insulin target tissues, the goal of this study was to evaluate the effects of 2 emerging bisphenols (BPS and BPF) on cytotoxicity, proliferation, myogenic differentiation, and insulin responsiveness in skeletal muscle cells. We tested this using a dose-response approach in C2C12 mouse and L6 rat myoblast cell lines. The results showed that C2C12 mouse myoblasts were more susceptible to bisphenols compared with L6 rat myoblasts. In both cell lines, bisphenol A was more cytotoxic, followed by BPF and BPS. C2C12 myoblast proliferation was higher upon BPF exposure at the 10−4 M dose and the fusion index was increased after exposure to either BPF or BPS at doses over 10−10 M. Exposure to BPS and BPF also reduced baseline expression of p-AKT (Thr) and p-GSK-3β, but not downstream effectors such as mTOR and glucose transporter-4. In conclusion, at noncytotoxic doses, BPS and BPF can alter myoblast cell proliferation, differentiation, and partially modulate early effectors of the insulin receptor signaling pathway. However, BPS or BPF short-term exposure evaluated here does not result in impaired insulin responsiveness.
A Novel Framework Using Remote Telesimulation With Standardized Parents to Improve Research Staff Preparedness for Informed Consent in Pediatric Critical Care Research*
Authors: LaMarra Denise , French Jaclyn , Bailey Christine , Sisko Martha T. , Coughlin-Wells Kerry , Agus Michael S. D. , Srinivasan Vijay , Nadkarni Vinay M. 
Published: July 2020

Objectives:
The Heart And Lung Failure—Pediatric INsulin Titration study was experiencing poor subject enrollment due to low rates of informed consent. Heart And Lung Failure—Pediatric INsulin Titration investigators collaborated with the Perelman School of Medicine Standardized Patient Program to explore the novel use of telesimulation with standardized parents to train research staff to approach parents of critically ill children for informed consent. We describe the feasibility, learner acceptance, and financial costs of this novel intervention and performed a post hoc analysis to determine if this intervention improved study consent rates.

Design:
Observational, comparative effectiveness study.

Setting:
Heart And Lung Failure—Pediatric INsulin Titration study enrolling sites.

Subjects:
Research staff (at the remote site).

Interventions:
Individual 90-minute Skype telesimulation sessions with standardized parent and simulation facilitator (at the training site).

Measurements and Main Results:
Forty telesimulation sessions with 79 Heart And Lung Failure—Pediatric INsulin Titration research staff (participants) at 24 remote sites were conducted. Despite some technical delays, 40 out of 40 simulations (100%) were completed. Based on feedback surveys, 100% of respondents agreed (81% strongly agreed) that telesimulation sessions achieved intended learning objectives to prepare research staff to approach parents of eligible critically ill children to obtain informed consent. Additionally, 100% of respondents agreed (74% strongly agreed) that they would use lessons from the telesimulation when approaching parents to obtain informed consent for research. Telesimulation with standardized parents achieved lower financial costs (approximately $85 per session) compared with traditional in-person site visits for training research staff. There was no significant improvement in study consent rates with the intervention (pre: 46% vs post: 48%; p = 0.78).

Conclusions:
Remote telesimulation with standardized parents is feasible, acceptable, and associated with lower financial costs to prepare research staff to obtain informed consent from parents of critically ill children eligible for clinical research trials. Despite this novel approach, Heart And Lung Failure—Pediatric INsulin Titration study consent rates did not improve, suggesting that other factors influence parental consent and decision making in complex multicenter clinical research trials.
Multi-scale analysis and modelling of collective migration in biological systems
Authors: Deutsch Andreas , Friedl Peter , Preziosi Luigi , Theraulaz Guy 
Published: July 2020

Collective migration has become a paradigm for emergent behaviour in systems of moving and interacting individual units resulting in coherent motion. In biology, these units are cells or organisms. Collective cell migration is important in embryonic development, where it underlies tissue and organ formation, as well as pathological processes, such as cancer invasion and metastasis. In animal groups, collective movements may enhance individuals' decisions and facilitate navigation through complex environments and access to food resources. Mathematical models can extract unifying principles behind the diverse manifestations of collective migration. In biology, with a few exceptions, collective migration typically occurs at a ‘mesoscopic scale’ where the number of units ranges from only a few dozen to a few thousands, in contrast to the large systems treated by statistical mechanics. Recent developments in multi-scale analysis have allowed linkage of mesoscopic to micro- and macroscopic scales, and for different biological systems. The articles in this theme issue on ‘Multi-scale analysis and modelling of collective migration’ compile a range of mathematical modelling ideas and multi-scale methods for the analysis of collective migration. These approaches (i) uncover new unifying organization principles of collective behaviour, (ii) shed light on the transition from single to collective migration, and (iii) allow us to define similarities and differences of collective behaviour in groups of cells and organisms. As a common theme, self-organized collective migration is the result of ecological and evolutionary constraints both at the cell and organismic levels. Thereby, the rules governing physiological collective behaviours also underlie pathological processes, albeit with different upstream inputs and consequences for the group.This article is part of the theme issue ‘Multi-scale analysis and modelling of collective migration in biological systems’.
Modelling collective cell motion: are on- and off-lattice models equivalent?
Authors: Nava-Sedeño Josué Manik , Voß-Böhme Anja , Hatzikirou Haralampos , Deutsch Andreas , Peruani Fernando 
Published: July 2020

Biological processes, such as embryonic development, wound repair and cancer invasion, or bacterial swarming and fruiting body formation, involve collective motion of cells as a coordinated group. Collective cell motion of eukaryotic cells often includes interactions that result in polar alignment of cell velocities, while bacterial patterns typically show features of apolar velocity alignment. For analysing the population-scale effects of these different alignment mechanisms, various on- and off-lattice agent-based models have been introduced. However, discriminating model-specific artefacts from general features of collective cell motion is challenging. In this work, we focus on equivalence criteria at the population level to compare on- and off-lattice models. In particular, we define prototypic off- and on-lattice models of polar and apolar alignment, and show how to obtain an on-lattice from an off-lattice model of velocity alignment. By characterizing the behaviour and dynamical description of collective migration models at the macroscopic level, we suggest the type of phase transitions and possible patterns in the approximative macroscopic partial differential equation descriptions as informative equivalence criteria between on- and off-lattice models.
This article is part of the theme issue ‘Multi-scale analysis and modelling of collective migration in biological systems’.
Collective dynamics of sperm cells
Authors: Schoeller Simon F. , Holt William V. , Keaveny Eric E. 
Published: July 2020

While only a single sperm may fertilize the egg, getting to the egg can be facilitated, and possibly enhanced, by sperm group dynamics. Examples range from the trains formed by wood mouse sperm to the bundles exhibited by echidna sperm. In addition, observations of wave-like patterns exhibited by ram semen are used to score prospective sample fertility for artificial insemination in agriculture. In this review, we discuss these experimental observations of collective dynamics, as well as describe recent mechanistic models that link the motion of individual sperm cells and their flagella to observed collective dynamics. Establishing this link in models involves negotiating the disparate time- and length scales involved, typically separated by a factor of 1000, to capture the dynamics at the greatest length scales affected by mechanisms at the shortest time scales. Finally, we provide some outlook on the subject, in particular, the open questions regarding how collective dynamics impacts fertility.This article is part of the theme issue ‘Multi-scale analysis and modelling of collective migration in biological systems’.
Autocrine inhibition of cell motility can drive epithelial branching morphogenesis in the absence of growth
Authors: Rens Elisabeth G. , Zeegers Mathé T. , Rabbers Iraes , Szabó András , Merks Roeland M. H. 
Published: July 2020

Epithelial branching morphogenesis drives the development of organs such as the lung, salivary gland, kidney and the mammary gland. It involves cell proliferation, cell differentiation and cell migration. An elaborate network of chemical and mechanical signals between the epithelium and the surrounding mesenchymal tissues regulates the formation and growth of branching organs. Surprisingly, when cultured in isolation from mesenchymal tissues, many epithelial tissues retain the ability to exhibit branching morphogenesis even in the absence of proliferation. In this work, we propose a simple, experimentally plausible mechanism that can drive branching morphogenesis in the absence of proliferation and cross-talk with the surrounding mesenchymal tissue. The assumptions of our mathematical model derive fromin vitroobservations of the behaviour of mammary epithelial cells. These data show that autocrine secretion of the growth factor TGFβ1 inhibits the formation of cell protrusions, leading to curvature-dependent inhibition of sprouting. Our hybrid cellular Potts and partial-differential equation model correctly reproduces the experimentally observed tissue-geometry-dependent determination of the sites of branching, and it suffices for the formation of self-avoiding branching structures in the absence and also in the presence of cell proliferation.This article is part of the theme issue ‘Multi-scale analysis and modelling of collective migration in biological systems’.
Rules of collective migration: from the wildebeest to the neural crest
Authors: Shellard Adam , Mayor Roberto 
Published: July 2020

Collective migration, the movement of groups in which individuals affect the behaviour of one another, occurs at practically every scale, from bacteria up to whole species' populations. Universal principles of collective movement can be applied at all levels. In this review, we will describe the rules governing collective motility, with a specific focus on the neural crest, an embryonic stem cell population that undergoes extensive collective migration during development. We will discuss how the underlying principles of individual cell behaviour, and those that emerge from a supracellular scale, can explain collective migration.This article is part of the theme issue ‘Multi-scale analysis and modelling of collective migration in biological systems’.
Collective invasion of glioma cells through OCT1 signalling and interaction with reactive astrocytes after surgery
Authors: Kim Yangjin , Lee Donggu , Lawler Sean 
Published: July 2020

Glioblastoma multiforme (GBM) is the most aggressive form of brain cancer with a short median survival time. GBM is characterized by the hallmarks of aggressive proliferation and cellular infiltration of normal brain tissue. miR-451 and its downstream molecules are known to play a pivotal role in regulation of the balance of proliferation and aggressive invasion in response to metabolic stress in the tumour microenvironment (TME). Surgery-induced transition in reactive astrocyte populations can play a significant role in tumour dynamics. In this work, we develop a multi-scale mathematical model of miR-451-LKB1-AMPK-OCT1-mTOR pathway signalling and individual cell dynamics of the tumour and reactive astrocytes after surgery. We show how the effects of fluctuating glucose on tumour cells need to be reprogrammed by taking into account the recent history of glucose variations and an AMPK/miR-451 reciprocal feedback loop. The model shows how variations in glucose availability significantly affect the activity of signalling molecules and, in turn, lead to critical cell migration. The model also predicts that microsurgery of a primary tumour induces phenotypical changes in reactive astrocytes and stem cell-like astrocytes promoting tumour cell proliferation and migration by Cxcl5. Finally, we investigated a new anti-tumour strategy by Cxcl5-targeting drugs.
This article is part of the theme issue ‘Multi-scale analysis and modelling of collective migration in biological systems’.
Dynamic heterogeneity influences the leader–follower dynamics during epithelial wound closure
Authors: Vishwakarma Medhavi , Thurakkal Basil , Spatz Joachim P. , Das Tamal 
Published: July 2020

Cells of epithelial tissue proliferate and pack together to attain an eventual density homeostasis. As the cell density increases, spatial distribution of velocity and force show striking similarity to the dynamic heterogeneity observed elsewhere in dense granular matter. While the physical nature of this heterogeneity is somewhat known in the epithelial cell monolayer, its biological relevance and precise connection to cell density remain elusive. Relevantly, we had demonstrated how large-scale dynamic heterogeneity in the monolayer stress field in the bulk could critically influence the emergence of leader cells at the wound margin during wound closure, but did not connect the observation to the corresponding cell density. In fact, numerous previous reports had essentially associated long-range force and velocity correlation with either cell density or dynamic heterogeneity, without any generalization. Here, we attempted to unify these two parameters under a single framework and explored their consequence on the dynamics of leader cells, which eventually affected the efficacy of collective migration and wound closure. To this end, we first quantified the dynamic heterogeneity by the peak height of four-point susceptibility. Remarkably, this quantity showed a linear relationship with cell density over many experimental samples. We then varied the heterogeneity, by changing cell density, and found this change altered the number of leader cells at the wound margin. At low heterogeneity, wound closure was slower, with decreased persistence, reduced coordination and disruptive leader–follower interactions. Finally, microscopic characterization of cell–substrate adhesions illustrated how heterogeneity influenced orientations of focal adhesions, affecting coordinated cell movements. Together, these results demonstrate the importance of dynamic heterogeneity in epithelial wound healing.
This article is part of the theme issue ‘Multi-scale analysis and modelling of collective migration in biological systems'.
3D Printed frames to enable reuse and improve the fit of N95 and KN95 respirators
Authors: McAvoy Malia , Bui Ai-Tram N. , Hansen Christopher , Plana Deborah , Said Jordan T. , Yu Zizi , Yang Helen , Freake Jacob , Van Christopher , Krikorian David , Cramer Avilash , Smith Leanne , Jiang Liwei , Lee Karen J. , Li Sara J. , Beller Brandon , Short Michael , Yu Sherry H. , Mostaghimi Arash , Sorger Peter K. , LeBoeuf Nicole R. 
Published: July 2020

ABSTRACTBackgroundIn response to supply shortages during the COVID-19 pandemic, N95 filtering facepiece respirators (FFRs or “masks”), which are typically single-use devices in healthcare settings, are routinely being used for prolonged periods and in some cases decontaminated under “reuse” and “extended use” policies. However, the reusability of N95 masks is often limited by degradation or breakage of elastic head bands and issues with mask fit after repeated use. The purpose of this study was to develop a frame for N95 masks, using readily available materials and 3D printing, which could replace defective or broken bands and improve fit.ResultsAn iterative design process yielded a mask frame consisting of two 3D-printed side pieces, malleable wire links that users press against their face, and cut lengths of elastic material that go around the head to hold the frame and mask in place. Volunteers (n= 41; average BMI= 25.5), of whom 31 were women, underwent qualitative fit with and without mask frames and one or more of four different brands of FFRs conforming to US N95 or Chinese KN95 standards. Masks passed qualitative fit testing in the absence of a frame at rates varying from 48 – 92% (depending on mask model and tester). For individuals for whom a mask passed testing, 75-100% (average = 86%) also passed testing with a frame holding the mask in place. Among users for whom a mask failed in initial fit testing, 41% passed using a frame. Success varied with mask model and across individuals.ConclusionsThe use of mask frames can prolong the lifespan of N95 and KN95 masks by serving as a substitute for broken or defective bands without adversely affecting fit. Frames also have the potential to improve fit for some individuals who cannot fit existing masks. Frames therefore represent a simple and inexpensive way of extending the life and utility of PPE in short supply. For clinicians and institutions interested in mask frames, designs and specifications are provided without restriction for use or modification. To ensure adequate performance in clinical settings, qualitative fit testing with user-specific masks and frames is required.
Daily Forecasting of New Cases for Regional Epidemics of Coronavirus Disease 2019 with Bayesian Uncertainty Quantification
Authors: Lin Yen Ting , Neumann Jacob , Miller Ely F. , Posner Richard G. , Mallela Abhishek , Safta Cosmin , Ray Jaideep , Thakur Gautam , Chinthavali Supriya , Hlavacek William S. 
Published: July 2020

AbstractTo increase situational awareness and support evidence-based policy-making, we formulated a mathematical model for COVID-19 transmission within a regional population. This compartmental model accounts for quarantine, self-isolation, social distancing, a non-exponentially distributed incubation period, asymptomatic individuals, and mild and severe forms of symptomatic disease. Using Bayesian inference, we have been calibrating region-specific models daily for consistency with new reports of confirmed cases from the 15 most populous metropolitan statistical areas in the United States and quantifying uncertainty in parameter estimates and predictions of future case reports. This online learning approach allows for early identification of new trends despite considerable variability in case reporting.Article Summary LineWe report models for regional COVID-19 epidemics and use of Bayesian inference to quantify uncertainty in daily predictions of expected reporting of new cases, enabling identification of new trends in surveillance data.
Working from a distance: Who can afford to stay home during COVID-19? Evidence from mobile device data
Authors: Dimke Christine , Lee Marissa , Bayham Jude 
Published: July 2020

AbstractAs the COVID-19 pandemic continues, local and state governments must weigh the costs and benefits of social distancing policy. However, the effectiveness of such policies depend on individuals’ willingness and ability to comply. We propose a simple method to infer sociodemographic heterogeneity in social distancing as measured by Safegraph mobile device data. We document evidence that people’s ability to work from home is a determinant of time spent at home since the beginning of the pandemic. On April 15th, census block groups that are more likely able to work from home spent 3 more hours at home compared to those who were not. We see supporting trends among block groups with differences in income and educational attainment.JELJ19, J69, Z00
Immunohistochemistry and Next Generation Sequencing are Complementary Tests in Identifying PTEN Abnormality in Endometrial Carcinoma Biopsies
Authors: Wang Linyuan , Piskorz Anna , Bosse Tjalling , Jimenez-Linan Mercedes , Rous Brian , Gilks C. Blake , Brenton James D. , Singh Naveena , Köbel Martin 
Published: July 2020

SummaryPTEN plays a central role in the pathogenesis of endometrial carcinoma. Previous studies reported a high interobserver reproducibility for the interpretation of PTEN immunohistochemistry (IHC). However, PTEN IHC and its interpretation remain challenging during laboratory practice. The purpose of this study was to reevaluate PTEN IHC pattern in direct comparison to next generation sequencing (NGS) in identifying PTEN abnormality. IHC and tagged-amplicon NGS PTEN sequencing was performed on 182 endometrial carcinoma biopsy/curetting samples from five centers (Barts, Calgary, Cambridge, Leiden, and Vancouver). Sensitivity, specificity and accuracy of PTEN IHC to predict loss of function (LOF) PTEN mutations were calculated. Abnormalities of PTEN in association with histotype and molecular subtype were assessed. A total of five PTEN IHC patterns were recorded: absent, subclonal loss, equivocal, reduced (relative to internal control) and retained. The absence of PTEN IHC has a sensitivity of 75.4% (95% CI 62.7 – 85.5%), a specificity of 84.6% (95% CI 76.2 – 90.9%), and accuracy of 81.2% (95% CI 74.4 – 86.9%) in predicting LOF PTEN mutation. PTEN abnormality by complementary interpretation of both assays was present in 91.9% of endometrial endometrioid carcinoma, grade 1, and significantly higher in endometrial endometrioid carcinomas of all grades compared to endometrial serous carcinoma (80.0% versus 19.4%, p<0.0001). PTEN abnormalities are common across all molecular subtypes of endometrioid carcinomas. Our data support complementary testing of both IHC and sequencing of PTEN to assess the PTEN status in endometrial carcinomas.